IndraLab

Statements


WDR48 affects USP46
19 | 74 40
WDR48 binds USP46.
19 | 46 35
19 | 37 17

No evidence text available

reach
"Intriguingly, we find that these structures resemble the USP46 and UAF1 complex structure, including the presence of the second binding site."

No evidence text available

reach
"We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the DUB to deubiquitinate and stabilize GLR-1 in vivo."

sparser
"Similar to USP1, human USP46 forms a complex with UAF1 and the activity of USP46 is stimulated by UAF1 ( xref )."

reach
"The scaffold protein UAF1 forms a complex with USP1, USP12, and USP46 that is essential for their activity."

reach
"UAF1 also binds and activates two other DUBs, USP12 and USP46 (19), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner (20, 21)."

sparser
"The USP46-WDR48 interface and the USP46-WDR48-Ub complex share nearly the same characteristics. xref The interface between USP46 and WDR20 is facilitated through both hydrophobic and hydrophilic contacts."

No evidence text available

No evidence text available
| 9 2

reach
"These recent structural and biochemical studies complement in vivo studies of the USP-46, WDR-48, and WDR-20 complex in C. elegans."

reach
"Total levels of WDR48 and USP46 were unchanged upon 4HT withdrawal (XREF_FIG) thus increased signal in the WDR48 ChIP at the p14 was not attributable to increased expression of the constituents of the USP46, WDR48, and WDR20 complex by EBNA3C."

reach
"The overall structure of the USP46-WDR48-WDR20 complex is very similar to that of the USP12-WDR48-WDR20 complex."

reach
"Thus, the steady-state localization of the USP46/UAF1/WDR20 complex was cytoplasmic, while the USP12/UAF1/WDR20 complex localized mainly to the plasma membrane (PM)."

reach
"Because USP46 and USP12 are highly homologous (~ 90% identity) and we could confirm a robust association with USP46 by Western blotting (discussed below), we chose to focus our subsequent attention on the USP46, WDR48, and WDR20 complex."

reach
"Because our TAP lysis procedure extracted both nuclear and cytoplasmic proteins (XREF_SUPPLEMENTARY), we wanted to ensure that the USP46, WDR48, and WDR20 complex subcellular localization was compatible with formation of a complex with EBNA3 proteins."

reach
"Together with data showing that co-expression of the USP-46, WDR-48, and WDR-20 complex reduces levels of ubiquitinated GLR-1, these results support a model wherein USP-46, when bound to WDR-48 and WDR-20, deubiquitinates GLR-1 and increases receptor stability and function in vivo."

reach
"To determine whether the USP46-UAF1-WDR20 complex regulates Wnt signaling in physiological contexts, we took a loss-of-function approach in Drosophila."

sparser
"USP46 is normally associated with its accessory proteins UAF1 and WDR20."

sparser
"These results indicate that USP46 does not associate with its accessory factor UAF1 or WDR20 when interacting with or deubiquitinating Cdt2 in high risk E6 transformed cells."
| 8

sparser
"In addition to USP1, two other DUBs, USP12 and USP46 interact with UAF1 [ xref ], but the UAF1-binding sites in these DUBs have not yet been mapped."

sparser
"Recent crystallographic studies demonstrate that UAF1 binds to a distinct site on USP12 or USP46 and, through an allosteric interaction, stimulates DUB activity ( xref ; xref )."

sparser
"In C. elegans , USP46 and USP12 both bind to USP1-associated factor 1 (UAF1/WDR48) and the binding dramatically enhances the activity of USP12 and USP46 ( xref , xref ; xref )."

sparser
"The mode of interaction of USP12 and USP46 with UAF1 is still unclear."

sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."

sparser
"UAF1 also interacts with DUBs USP12 and USP46 ( García-Santisteban et al., 2013 ) and, thus, both genes also could be involved in senescence."

sparser
"P65 interacted with USP12, USP46 and UAF1 in both resting and LPS-stimulated macrophages, but exhibited no association with USP1 (Fig.  xref )."

sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
WDR48 binds USP1 and USP46. 2 / 2
| 2

sparser
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."

sparser
"Also, UAF1 can interact with USP1 and USP46 in addition to USP12 [ xref ]."

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
| 1

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme ( xref and xref )."
WDR48 activates USP46.
| 24 5
WDR48 activates USP46. 10 / 27
| 22 5

reach
"WDR48 stimulates the activity of the deubiquitylases USP1, USP12 and USP46."

reach
"USP12 and USP46, consisting of only a USP domain [4], share 88% amino acid sequence homology and are potentiated by WDR48, WDR20, and DMWD [8, 9, 10]."

reach
"For example, USP1, USP12, and USP46 are activated by the WD40-repeat containing UAF1, and USP7 is activated by GMPS (Cohn et al., 2007, 2009; Faesen et al., 2011; van der Knaap et al., 2005)."

sparser
"This study confirmed that the modulator UAF1 activates USP1, USP12, and USP46, and GMPS activates USP7."

reach
"Together, UAF1 and WDR20 are able to synergistically stimulate the enzymatic activities of USP12 and USP46 to a peak level."

reach
"WDR48, with the high score in our LC-MS/MS results, is reported as a cofactor to increase the enzymatic activity of USP1, USP12 and USP46, but could not modify the affinity of the DUBs and their subst[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Therefore, this suggests that for some USPs the KG FP reagent may be a better substrate, and provide more relevant kinetic parameters.This study confirmed that the modulator UAF1 activates USP1, USP12[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"However, a structural comparison of the enzyme in these two post-reaction forms revealed few conformational differences, leaving the mechanism of USP46 activation by UAF1 elusive."

reach
"WDR48 stimulates the activity of three DUBs, USP12, USP46 and USP1, a DUB which regulates the Fanconi anemia DNA damage pathway."

reach
"Given the distinct binding mode elucidated here, it is less straightforward to reconcile this structure with direct active-site modulation, yet we propose a mechanism centered on WDR48 dependent USP s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
WDR48 activates mutated USP46. 1 / 1
| 1

reach
"These findings indicate that Usp46, and its allosteric regulators Uaf1 and Wdr20, promote Wingless signaling in target cells in the wing imaginal disc.We further characterized Usp46 mutant cells in the wing disc that were generated by combining CRISPR-based mutagenesis with tissue-specific expression of Cas9 and Usp46 guide RNAs."
WDR48 bound to WDR20 activates USP46. 1 / 1
| 1

reach
"We and others previously showed that the WD40-repeat proteins WDR-48 and WDR-20 bind to and stimulate the catalytic activity of USP-46."
WDR48 increases the amount of USP46.
| 2
WDR48 increases the amount of USP46. 2 / 2
| 2

reach
"Of note, this analysis also revealed that Wdr20, and to a lesser extent Uaf1, stabilized Usp46, as knockdown of either Uaf1 or Wdr20 reduced Usp46 levels (Fig. 7C)."

reach
"Conversely, overexpression of either Wdr20 or Uaf1 increased the levels of Usp46 (Fig. S22)."
WDR48 deubiquitinates USP46.
| 1
WDR48 deubiquitinates USP46. 1 / 1
| 1

reach
"The E1 protein from anogenital HPV types interacts with the UAF1 associated deubiquitinating enzymes USP1, USP12, and USP46 to stimulate replication of the viral genome."
WDR48 decreases the amount of USP46.
| 1
WDR48 decreases the amount of USP46. 1 / 1
| 1

reach
"Consistent with this result, loss of UAF1 has been previously shown to decrease USP46 levels , and we observed a similar effect when we knocked down UAF1 (Supplementary Fig. 1B)."
USP46 affects WDR48
19 | 49 35
USP46 binds WDR48.
19 | 46 35
19 | 37 17

No evidence text available

reach
"Intriguingly, we find that these structures resemble the USP46 and UAF1 complex structure, including the presence of the second binding site."

No evidence text available

reach
"We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the DUB to deubiquitinate and stabilize GLR-1 in vivo."

sparser
"Similar to USP1, human USP46 forms a complex with UAF1 and the activity of USP46 is stimulated by UAF1 ( xref )."

reach
"The scaffold protein UAF1 forms a complex with USP1, USP12, and USP46 that is essential for their activity."

reach
"UAF1 also binds and activates two other DUBs, USP12 and USP46 (19), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner (20, 21)."

sparser
"The USP46-WDR48 interface and the USP46-WDR48-Ub complex share nearly the same characteristics. xref The interface between USP46 and WDR20 is facilitated through both hydrophobic and hydrophilic contacts."

No evidence text available

No evidence text available
| 9 2

reach
"These recent structural and biochemical studies complement in vivo studies of the USP-46, WDR-48, and WDR-20 complex in C. elegans."

reach
"Total levels of WDR48 and USP46 were unchanged upon 4HT withdrawal (XREF_FIG) thus increased signal in the WDR48 ChIP at the p14 was not attributable to increased expression of the constituents of the USP46, WDR48, and WDR20 complex by EBNA3C."

reach
"The overall structure of the USP46-WDR48-WDR20 complex is very similar to that of the USP12-WDR48-WDR20 complex."

reach
"Thus, the steady-state localization of the USP46/UAF1/WDR20 complex was cytoplasmic, while the USP12/UAF1/WDR20 complex localized mainly to the plasma membrane (PM)."

reach
"Because USP46 and USP12 are highly homologous (~ 90% identity) and we could confirm a robust association with USP46 by Western blotting (discussed below), we chose to focus our subsequent attention on the USP46, WDR48, and WDR20 complex."

reach
"Because our TAP lysis procedure extracted both nuclear and cytoplasmic proteins (XREF_SUPPLEMENTARY), we wanted to ensure that the USP46, WDR48, and WDR20 complex subcellular localization was compatible with formation of a complex with EBNA3 proteins."

reach
"Together with data showing that co-expression of the USP-46, WDR-48, and WDR-20 complex reduces levels of ubiquitinated GLR-1, these results support a model wherein USP-46, when bound to WDR-48 and WDR-20, deubiquitinates GLR-1 and increases receptor stability and function in vivo."

reach
"To determine whether the USP46-UAF1-WDR20 complex regulates Wnt signaling in physiological contexts, we took a loss-of-function approach in Drosophila."

sparser
"USP46 is normally associated with its accessory proteins UAF1 and WDR20."

sparser
"These results indicate that USP46 does not associate with its accessory factor UAF1 or WDR20 when interacting with or deubiquitinating Cdt2 in high risk E6 transformed cells."
| 8

sparser
"In addition to USP1, two other DUBs, USP12 and USP46 interact with UAF1 [ xref ], but the UAF1-binding sites in these DUBs have not yet been mapped."

sparser
"Recent crystallographic studies demonstrate that UAF1 binds to a distinct site on USP12 or USP46 and, through an allosteric interaction, stimulates DUB activity ( xref ; xref )."

sparser
"In C. elegans , USP46 and USP12 both bind to USP1-associated factor 1 (UAF1/WDR48) and the binding dramatically enhances the activity of USP12 and USP46 ( xref , xref ; xref )."

sparser
"The mode of interaction of USP12 and USP46 with UAF1 is still unclear."

sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."

sparser
"UAF1 also interacts with DUBs USP12 and USP46 ( García-Santisteban et al., 2013 ) and, thus, both genes also could be involved in senescence."

sparser
"P65 interacted with USP12, USP46 and UAF1 in both resting and LPS-stimulated macrophages, but exhibited no association with USP1 (Fig.  xref )."

sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
WDR48 binds USP1 and USP46. 2 / 2
| 2

sparser
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."

sparser
"Also, UAF1 can interact with USP1 and USP46 in addition to USP12 [ xref ]."

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
| 1

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme ( xref and xref )."
USP46 activates WDR48.
| 2
USP46 activates WDR48. 2 / 2
| 2

reach
"It raises the possibility that a targeted knockout of Uaf1 in granulosa cells might lead to infertility in female mice, which could provide further insights into UAF1’s specific functions in female reproductive biology.UAF1 acts as a cofactor for USP1, USP12, and USP46, enhancing their deubiquitinase activity by forming stable UAF1/USP protein complexes.14 18 Defective spermiogenesis in Uaf1 sKO mice necessitated the identification of a DUB critical for this process."

reach
"These results indicated that UAF1 suppressed JEV replication.As the cofactor of USP1, USP12, and USP46, UAF1 could enhance their deubiquitinase activity by forming stable UAF1/USP protein complexes (6, 38)."
USP46 deubiquitinates WDR48.
| 1
USP46 deubiquitinates WDR48. 1 / 1
| 1

reach
"Usp12 and Usp46 deubiquitinate both H2A and H2B and Uaf-1 is required for this reaction [XREF_BIBR]."
USP12 affects USP46
4 | 19 30
USP12 binds USP46.
4 | 17 30
4 | 17 11

reach
"EBNA3A and EBNA3B target the USP46 and USP12 complexes in LCLs."

reach
"H. Model : UAF1 mediates the interaction between USP1 and RAD51AP1.of USP12 and USP46, 2 DUBs that also associate with UAF1,26 did not significantly affect the RAD51AP1 stability, suggesting that the effect is specific to the USP1-UAF1 complex.Mapping of the UAF1 interacting region of RAD51AP1In order to specifically determine the functional significance of the UAF1-RAD51AP1 interaction, we sought to identify the residues within RAD51AP1 required for interacting with UAF1."

reach
"Our data demonstrates a proof-of-principle for USP12 and USP46 complex targeting in PC and uncovers additional mechanisms of galeterone activity."

sparser
"WDR48, a WD40 repeat-containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity."

reach
"Similarly galeterone inhibition did not have a significant effect on transcript levels of USP12 and USP46 complex members UAF1 (adj. p = 0.4) and WDR20 (adj. p = 0.25)."

reach
"Conversely, in the CWR22Rv1 cell line silencing AR FL alone decreased galeterone efficiency by 4 fold compared to SCR control and silencing USP12 or USP12 and USP46 complex members had no significant effect on galeterone efficacy."

reach
"Although the PHLLP1 and PHLLP2 phosphatases have been reported to be components of the USP46 and USP12 complexes, they were not detectably associated with EBNA3 complexes, likely because these phosphatases are predominantly membrane associated [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."

reach
"Membrane associated USP46 and USP12 complexes have been implicated in regulating membrane trafficking of receptors, including Notch1 and GLR1 [XREF_BIBR, XREF_BIBR]."

reach
"We therefore tested C527 for its ability to inhibit the purified USP12 and USP46 complex or other DUBs."

reach
"C527 inhibited the DUB activity of the USP12 and USP46 complex and other DUB enzymes in vitro."
| 8

sparser
"In addition to USP1, two other DUBs, USP12 and USP46 interact with UAF1 [ xref ], but the UAF1-binding sites in these DUBs have not yet been mapped."

sparser
"Recent crystallographic studies demonstrate that UAF1 binds to a distinct site on USP12 or USP46 and, through an allosteric interaction, stimulates DUB activity ( xref ; xref )."

sparser
"In C. elegans , USP46 and USP12 both bind to USP1-associated factor 1 (UAF1/WDR48) and the binding dramatically enhances the activity of USP12 and USP46 ( xref , xref ; xref )."

sparser
"The mode of interaction of USP12 and USP46 with UAF1 is still unclear."

sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."

sparser
"UAF1 also interacts with DUBs USP12 and USP46 ( García-Santisteban et al., 2013 ) and, thus, both genes also could be involved in senescence."

sparser
"P65 interacted with USP12, USP46 and UAF1 in both resting and LPS-stimulated macrophages, but exhibited no association with USP1 (Fig.  xref )."

sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
USP1 binds USP12 and USP46. 2 / 2
| 2

sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."

sparser
"UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46."
| 2

sparser
"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [ xref , xref ]."

sparser
"Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1."

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
DMWD binds USP12 and USP46. 1 / 1
| 1

sparser
"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
USP12 binds USP46 and TBK1. 1 / 1
| 1

sparser
"In addition, USP12 and USP46 were not associated with TBK1 ( xref )."
USP12 inhibits USP46.
| 1
USP12 inhibits USP46. 1 / 1
| 1

reach
"We propose a mechanism by which Usp12 suppresses HD related neurodegeneration via induction of autophagy."
USP12 activates USP46.
| 1
USP12 bound to WDR48 activates USP46. 1 / 1
| 1

reach
"In C. elegans, USP46 and USP12 both bind to USP1 associated factor 1 (UAF1 and WDR48) and the binding dramatically enhances the activity of USP12 and USP46."
USP46 affects USP12
4 | 18 30
USP46 binds USP12.
4 | 17 30
4 | 17 11

reach
"EBNA3A and EBNA3B target the USP46 and USP12 complexes in LCLs."

reach
"H. Model : UAF1 mediates the interaction between USP1 and RAD51AP1.of USP12 and USP46, 2 DUBs that also associate with UAF1,26 did not significantly affect the RAD51AP1 stability, suggesting that the effect is specific to the USP1-UAF1 complex.Mapping of the UAF1 interacting region of RAD51AP1In order to specifically determine the functional significance of the UAF1-RAD51AP1 interaction, we sought to identify the residues within RAD51AP1 required for interacting with UAF1."

reach
"Our data demonstrates a proof-of-principle for USP12 and USP46 complex targeting in PC and uncovers additional mechanisms of galeterone activity."

sparser
"WDR48, a WD40 repeat-containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity."

reach
"Similarly galeterone inhibition did not have a significant effect on transcript levels of USP12 and USP46 complex members UAF1 (adj. p = 0.4) and WDR20 (adj. p = 0.25)."

reach
"Conversely, in the CWR22Rv1 cell line silencing AR FL alone decreased galeterone efficiency by 4 fold compared to SCR control and silencing USP12 or USP12 and USP46 complex members had no significant effect on galeterone efficacy."

reach
"Although the PHLLP1 and PHLLP2 phosphatases have been reported to be components of the USP46 and USP12 complexes, they were not detectably associated with EBNA3 complexes, likely because these phosphatases are predominantly membrane associated [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."

reach
"Membrane associated USP46 and USP12 complexes have been implicated in regulating membrane trafficking of receptors, including Notch1 and GLR1 [XREF_BIBR, XREF_BIBR]."

reach
"We therefore tested C527 for its ability to inhibit the purified USP12 and USP46 complex or other DUBs."

reach
"C527 inhibited the DUB activity of the USP12 and USP46 complex and other DUB enzymes in vitro."
| 8

sparser
"In addition to USP1, two other DUBs, USP12 and USP46 interact with UAF1 [ xref ], but the UAF1-binding sites in these DUBs have not yet been mapped."

sparser
"Recent crystallographic studies demonstrate that UAF1 binds to a distinct site on USP12 or USP46 and, through an allosteric interaction, stimulates DUB activity ( xref ; xref )."

sparser
"In C. elegans , USP46 and USP12 both bind to USP1-associated factor 1 (UAF1/WDR48) and the binding dramatically enhances the activity of USP12 and USP46 ( xref , xref ; xref )."

sparser
"The mode of interaction of USP12 and USP46 with UAF1 is still unclear."

sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."

sparser
"UAF1 also interacts with DUBs USP12 and USP46 ( García-Santisteban et al., 2013 ) and, thus, both genes also could be involved in senescence."

sparser
"P65 interacted with USP12, USP46 and UAF1 in both resting and LPS-stimulated macrophages, but exhibited no association with USP1 (Fig.  xref )."

sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
USP1 binds USP12 and USP46. 2 / 2
| 2

sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."

sparser
"UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46."
| 2

sparser
"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [ xref , xref ]."

sparser
"Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1."

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
DMWD binds USP12 and USP46. 1 / 1
| 1

sparser
"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
USP12 binds USP46 and TBK1. 1 / 1
| 1

sparser
"In addition, USP12 and USP46 were not associated with TBK1 ( xref )."
USP46 activates USP12.
| 1
USP46 bound to WDR48 activates USP12. 1 / 1
| 1

reach
"In C. elegans, USP46 and USP12 both bind to USP1 associated factor 1 (UAF1 and WDR48) and the binding dramatically enhances the activity of USP12 and USP46."
WDR20 affects USP46
13 | 31 7
WDR20 binds USP46.
13 | 17 6
13 | 8 1

sparser
"These findings imply that the complex formation and USP46 activity regulation are significantly influenced by the residues participating in the USP46-WDR20 interaction ( xref ). xref "

No evidence text available

No evidence text available

reach
"The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans."

No evidence text available

No evidence text available

reach
"We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the DUB to deubiquitinate and stabilize GLR-1 in vivo."

No evidence text available

No evidence text available

No evidence text available
| 9 2

reach
"These recent structural and biochemical studies complement in vivo studies of the USP-46, WDR-48, and WDR-20 complex in C. elegans."

reach
"Total levels of WDR48 and USP46 were unchanged upon 4HT withdrawal (XREF_FIG) thus increased signal in the WDR48 ChIP at the p14 was not attributable to increased expression of the constituents of the USP46, WDR48, and WDR20 complex by EBNA3C."

reach
"The overall structure of the USP46-WDR48-WDR20 complex is very similar to that of the USP12-WDR48-WDR20 complex."

reach
"Thus, the steady-state localization of the USP46/UAF1/WDR20 complex was cytoplasmic, while the USP12/UAF1/WDR20 complex localized mainly to the plasma membrane (PM)."

reach
"Because USP46 and USP12 are highly homologous (~ 90% identity) and we could confirm a robust association with USP46 by Western blotting (discussed below), we chose to focus our subsequent attention on the USP46, WDR48, and WDR20 complex."

reach
"Because our TAP lysis procedure extracted both nuclear and cytoplasmic proteins (XREF_SUPPLEMENTARY), we wanted to ensure that the USP46, WDR48, and WDR20 complex subcellular localization was compatible with formation of a complex with EBNA3 proteins."

reach
"Together with data showing that co-expression of the USP-46, WDR-48, and WDR-20 complex reduces levels of ubiquitinated GLR-1, these results support a model wherein USP-46, when bound to WDR-48 and WDR-20, deubiquitinates GLR-1 and increases receptor stability and function in vivo."

reach
"To determine whether the USP46-UAF1-WDR20 complex regulates Wnt signaling in physiological contexts, we took a loss-of-function approach in Drosophila."

sparser
"USP46 is normally associated with its accessory proteins UAF1 and WDR20."

sparser
"These results indicate that USP46 does not associate with its accessory factor UAF1 or WDR20 when interacting with or deubiquitinating Cdt2 in high risk E6 transformed cells."
| 2

sparser
"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [ xref , xref ]."

sparser
"Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
WDR20 activates USP46.
| 12 1
WDR20 activates USP46. 10 / 11
| 10 1

reach
"Although mammalian USP46 and USP12 DUB activity can be stimulated by two proteins UAF-1 and WDR20, the C. elegans homologs of these genes have not yet been identified."

reach
"USP12 and USP46, consisting of only a USP domain [4], share 88% amino acid sequence homology and are potentiated by WDR48, WDR20, and DMWD [8, 9, 10]."

reach
"Both WDR48 and WDR20 stimulate USP12 and USP46 catalytic activity (k cat) without increasing substrate binding affinity, suggesting that the WDR proteins may affect DUB activity via a novel structural mechanism."

reach
"WDR20 and UAF1 potentiate the activity of USP12 and USP46 by allosterically increasing their catalytic efficiency without increasing their substrate-binding affinity ."

reach
"Interestingly, the Caenorhabditis elegans homologs of WDR20 and WDR48 (also known as UAF1) can bind to and activate USP46."

reach
"In addition, whereas USP1 cannot interact with WDR20, USP12, and USP46 may; further WDR48 and WDR20 can both independently and cooperatively stimulate the activities of USP12 and USP46."

reach
"We found that increased expression of WDR-48, but not WDR-20, promotes USP-46 abundance in mammalian cells in culture and in C. elegans neurons in vivo Inhibition of the proteasome increased USP-46 abundance, and this effect was non additive with increased WDR-48 expression."

reach
"Together, UAF1 and WDR20 are able to synergistically stimulate the enzymatic activities of USP12 and USP46 to a peak level."

reach
"Interestingly, USP12 and USP46 are activated by two β-propeller proteins, UAF1, and WDR20."

reach
"These findings raised the possibility that, like their yeast counterparts, human UAF1 and WDR20 might modulate subcellular localization of USP12 and USP46 and, furthermore, that cofactor binding might[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
WDR20 bound to WDR48 activates USP46. 2 / 2
| 2

reach
"Indeed, it has been demonstrated that the binding of WDR20 and WDR48 synergistically activates USP46 39."

reach
"We found that the WD40-repeat proteins WDR-20 and WDR-48 bind and stimulate the catalytic activity of USP-46."
WDR20 increases the amount of USP46.
| 2
WDR20 increases the amount of USP46. 2 / 2
| 2

reach
"Conversely, overexpression of either Wdr20 or Uaf1 increased the levels of Usp46 (Fig. S22)."

reach
"Of note, this analysis also revealed that Wdr20, and to a lesser extent Uaf1, stabilized Usp46, as knockdown of either Uaf1 or Wdr20 reduced Usp46 levels (Fig. 7C)."
USP46 affects PHLPP1
13 1 | 24 10
USP46 binds PHLPP1.
13 | 6 10
13 | 4 10

sparser
"USP46 interacts with PHLPP in cells."

sparser
"Co-immunoprecipitation experiments showed that only USP46 specifically interacted with PHLPP1 in transfected 293T cells whereas other DUBs including USP7 and USP16 failed to binding PHLPP1, thus, demonstrating the specificity of USP46-mediated interaction ( xref )."

sparser
"Furthermore, the interaction between both endogenous PHLPP isoforms and USP46 was readily detected in DLD1 cells ( xref )."

No evidence text available

reach
"USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP in vitro and in cells."

sparser
"In CRC, a mutation in the protein WD repeat domain 48, required for interaction between PHLPP1 and USP12, resulted in PHLPP1 downregulation and consequent increase in AKT signaling ( Gangula and Maddi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"To determine if the interaction of PHLPP and USP46 is required for USP46-mediated increase of PHLPP expression, the full-length PHLPP1 or the USP46 binding-deficient Δ1139 mutant was co-expressed with USP46."

No evidence text available

No evidence text available

reach
"USP46 interacts with PHLPP in cells."
USP46 binds PHLPP1 and leucine. 1 / 1
| 1

reach
"Recently, a proteomic study on deubiquitinating enzymes and their associated protein complexes demonstrated that USP46 interacts with PHLPP and SCOP (PH-domain leucine rich repeat protein phosphatase and suprachiasmatic nucleus circadian oscillatory protein), which are members of the of Ser/Thr family of protein phosphatases XREF_BIBR."
USP46 binds PHLPP1 and 293T. 1 / 1
| 1

reach
"Co-immunoprecipitation experiments showed that only USP46 specifically interacted with PHLPP1 in transfected 293T cells whereas other DUBs including USP7 and USP16 failed to binding PHLPP1, thus, demonstrating the specificity of USP46 mediated interaction (XREF_FIG)."
USP46 activates PHLPP1.
| 7
USP46 activates PHLPP1. 7 / 7
| 7

reach
"If USP46 enhances the stability of PHLPP1, then human tumors with downregulation of PHLPP1 protein might also have decreased expression of USP46."

reach
"As previously described, USP46 mediated PHLPP stability in colon cancer through AKT inaction, indicating a novel mechanism of the USP46-AKT axis in tumor regulation."

reach
"Functionally, USP46 mediated stabilization of PHLPP and the subsequent inhibition of Akt result in a decrease in cell proliferation and tumorigenesis of colon cancer cells in vivo."

reach
"USP46 enhances PHLPP mediated negative regulation of Akt in cells."

reach
"Furthermore, knockdown of USP46 attenuated the ability of PHLPP1 to dephosphorylate Akt and to inhibit cell proliferation (XREF_FIG)."

reach
"USP46 potentiates the tumor suppressor function of PHLPP1 in vivo."

reach
"More importantly, co-expression of USP46 markedly enhanced the ability of PHLPP1 to suppress tumor formation (XREF_FIG)."
USP46 deubiquitinates PHLPP1.
1 | 4
USP46 deubiquitinates PHLPP1. 4 / 4
1 | 3

"SP1 [137] and <span class="match term0">USP46</span> [138] are other DUBs known to deubiquitinate <span class="match term1">PHLPP1</span>"

reach
"Emerging studies have reported that USP46 could deubiquitinate and reduce proteasome-mediated degradation of PHLPP, a family member of Ser/Thr protein phosphatases that acts as a tumor suppressor by n[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Previous research has shown that USP46 antagonized AKT activity by deubiquitinating PHLPP1 in colorectal cancer (15)."

reach
"USP46 inhibits AKT signaling by antagonizing PHLPP1 ubiquitination, and inhibits LC cell proliferation under normal growing environment and radiation-induced DNA damage."
Modified USP46 leads to the deubiquitination of PHLPP1. 1 / 1
| 1

reach
"Overexpression of WT USP46 significantly decreased the amount of ubiquitination of PHLPP1 both basally and after MG-132 treatment, while the catalytically inactive mutant USP46 had no effect (XREF_FIG)."
USP46 ubiquitinates PHLPP1.
| 4
USP46 ubiquitinates PHLPP1. 4 / 4
| 4

reach
"USP46 directly regulates the ubiquitination of PHLPP1."

reach
"Here, we investigated whether USP46 directly regulates the level of PHLPP1 ubiquitination in vitro and in cells."

reach
"Previous research has shown that USP46 antagonized AKT activity by deubiquitinating PHLPP1 in colorectal cancer (15)."

reach
"In general, USP46 can inhibits AKT activity by deubiquitinating PHLPP1, inhibits cell proliferation and DNA damage, thus, it increases the radiation sensitivity (19) ( Figure 3 and Table 1 ).4.2.3 Transcriptional regulation."
USP46 increases the amount of PHLPP1.
| 2
USP46 increases the amount of PHLPP1. 2 / 2
| 2

reach
"To determine if the interaction of PHLPP and USP46 is required for USP46 mediated increase of PHLPP expression, the full-length PHLPP1 or the USP46 binding deficient Delta1139 mutant was co-expressed with USP46."

reach
"Knockdown of USP46 in HCT116 cells has been observed to decrease the levels of PHLPP isoforms and, consequently, contribute to hypoxia-induced drug resistance in CRC[83]."
USP46 decreases the amount of PHLPP1.
| 1
USP46 decreases the amount of PHLPP1. 1 / 1
| 1

reach
"By stabilizing the expression of PHLPP, USP46 negatively regulates Akt activity in cells and in vivo."
E6 affects USP46
1 | 2 42
E6 binds USP46.
1 | 41
| 37

sparser
"Therefore, a specific modification on either protein or a cellular or viral chaperone may be necessary for the formation of the complex, but once formed, such an E6:USP46 complex is stable and catalytically active."

sparser
"We and others have shown that Cdt2 is degraded by ubiquitination by specific E3 ubiquitin ligases [ xref , xref ], making it plausible that the deubiquitination of Cdt2 by E6:USP46 leads to the stabilization of Cdt2."

sparser
"Stabilization of Cdt2 by E6:USP46 needs three prerequisites: (a) interaction of Cdt2 with E6:USP46, (b) recognition of Cdt2 by its E3 ubiquitin ligases and (c) the presence on Cdt2 of sites of polyubiquitination."

sparser
"We find that E6-USP46 contributes to the activation of EGFR by inducing epigenetic changes on the DNA by degrading the Set8 protein."

sparser
"To determine if the stabilization of Cdt2 by E6-USP46 alters Cdt2 substrates in cervical cancers, we checked the expression of Set8 in cancer biopsies."

sparser
"E6-USP46 Mediated Stabilization of Cdt2 Leads to Set8 Degradation and Loss of H4K20 Methylation in HPV Positive Cancers."

sparser
"Thus E6 and USP46 interacted with each other directly."

sparser
"Recently, it was demonstrated that HR HPV-16, -18 and -31 E6 bind to USP46, but that no interactions were seen with the LR HPV types [ xref ]."

sparser
"Thus in vitro , E6 interacts with USP46 and promotes the latter’s interaction with Cdt2."

sparser
"To test whether E6 and USP46 can interact with each other independent of other cellular proteins, a column with bacterial GST-16E6 was incubated with bacterially produced His-USP46."
E6 binds USP46 and DTL. 3 / 3
| 3

sparser
"The elution profile also suggests that the Cdt2 associates with E6-USP46, as a low-affinity substoichiometric substrate rather than as a core member of the E6-USP46 complex."

sparser
"In Hela cells, E6 is associates with E6AP and p53, and now we find that the E6 protein also associates with USP46 and Cdt2."

sparser
"We propose that the E6-USP46 interaction promotes the tripartite E6-USP46-Cdt2 complex either due to allosteric changes in USP46, or because Cdt2 interacts simultaneously with sites on E6 and USP46 ( xref )."
E6 binds USP46. 1 / 1
1 |

No evidence text available
E6 binds UBE3A, TP53, and USP46. 1 / 1
| 1

sparser
"E6 associates specifically with USP46+Cdt2 independent of E6AP, p53 and USP46 accessory proteins."
E6 activates USP46.
| 2 1
E6 activates USP46. 3 / 3
| 2 1

reach
"In conclusion, E6 causes degradation of Set8 and modifications in gene regulation in HPV-transformed cells, increases the deubiquitinase activity of USP46, and stabilizes Cdt2 by using numerous sites on Cdt2."

reach
"The presence of oncogenic E6 enables the USP46 deubiquitinase to enter the nucleus and interact with Cdt2, an event that causes the reversal of CRL1 Fbxo11 -mediated ubiquitination, leading to Cdt2 st[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Third, does pure recombinant E6 activate recombinant USP46 in the complete absence of known cellular activators of USP46 like UAF1 and WDR20?"
USP46 affects WDR20
13 | 17 6
13 | 8 1

sparser
"These findings imply that the complex formation and USP46 activity regulation are significantly influenced by the residues participating in the USP46-WDR20 interaction ( xref ). xref "

No evidence text available

No evidence text available

reach
"The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans."

No evidence text available

No evidence text available

reach
"We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the DUB to deubiquitinate and stabilize GLR-1 in vivo."

No evidence text available

No evidence text available

No evidence text available
| 9 2

reach
"These recent structural and biochemical studies complement in vivo studies of the USP-46, WDR-48, and WDR-20 complex in C. elegans."

reach
"Total levels of WDR48 and USP46 were unchanged upon 4HT withdrawal (XREF_FIG) thus increased signal in the WDR48 ChIP at the p14 was not attributable to increased expression of the constituents of the USP46, WDR48, and WDR20 complex by EBNA3C."

reach
"The overall structure of the USP46-WDR48-WDR20 complex is very similar to that of the USP12-WDR48-WDR20 complex."

reach
"Thus, the steady-state localization of the USP46/UAF1/WDR20 complex was cytoplasmic, while the USP12/UAF1/WDR20 complex localized mainly to the plasma membrane (PM)."

reach
"Because USP46 and USP12 are highly homologous (~ 90% identity) and we could confirm a robust association with USP46 by Western blotting (discussed below), we chose to focus our subsequent attention on the USP46, WDR48, and WDR20 complex."

reach
"Because our TAP lysis procedure extracted both nuclear and cytoplasmic proteins (XREF_SUPPLEMENTARY), we wanted to ensure that the USP46, WDR48, and WDR20 complex subcellular localization was compatible with formation of a complex with EBNA3 proteins."

reach
"Together with data showing that co-expression of the USP-46, WDR-48, and WDR-20 complex reduces levels of ubiquitinated GLR-1, these results support a model wherein USP-46, when bound to WDR-48 and WDR-20, deubiquitinates GLR-1 and increases receptor stability and function in vivo."

reach
"To determine whether the USP46-UAF1-WDR20 complex regulates Wnt signaling in physiological contexts, we took a loss-of-function approach in Drosophila."

sparser
"USP46 is normally associated with its accessory proteins UAF1 and WDR20."

sparser
"These results indicate that USP46 does not associate with its accessory factor UAF1 or WDR20 when interacting with or deubiquitinating Cdt2 in high risk E6 transformed cells."
| 2

sparser
"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [ xref , xref ]."

sparser
"Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."

sparser
"Meanwhile, results of the log-rank test also showed that the high AC112220.2, USP46-AS1, AL450326.1, SUCLG2-AS1, FGD5-AS1, AC018647.2 and AC015922.2 expression groups had remarkably longer DFS than their respective low expression groups (Figure xref )."

sparser
"Expression of LOC441179 , PON2 and USP46AS1 in glioma cells."

sparser
"Results of the log-rank test showed that the high expression groups of AC112220.2, AL391121.1, USP46-AS1, AL450326.1, SUCLG2-AS1, RAP2C-AS1, FGD5-AS1, AC018647.2 and AC015922.2 had significantly longer OS than their respective low expression groups (Figure xref )."

sparser
"qRT‐PCR was performed to investigate the expression of LOC441179 , PON2 and USP46AS1 in glioma cells compared to control cells."

sparser
"In this study, we found that several lncRNAs, including FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, ENSG00000271020, AC112220.2, AC018647.2, AC015922.2, MID1IP1-AS1, AL731577.2 and AL450326.1 were co-expressed with VHL, and their expression were positively correlated with VHL expression."

sparser
"Besides, the analysis results of catRAPID showed that AC112220.2, AL391121.1, USP46-AS1, AL450326.1, MID1IP1-AS1, SUCLG2-AS1, RAP2C-AS1, FGD5-AS1, AC018647.2 and AC015922.2 have a certain binding potential with VHL protein."

sparser
"Moreover, results of the log-rank test showed that high expression groups of AC112220.2, AL391121.1, USP46-AS1, AL450326.1, SUCLG2-AS1, RAP2C-AS1, FGD5-AS1, AC018647.2 and AC015922.2 had significantly longer OS than their respective low expression groups, and high AC112220.2, USP46-AS1, AL450326.1, SUCLG2-AS1, FGD5-AS1, AC018647.2 and AC015922.2 expression groups had remarkably longer DFS than their respective low expression groups."

sparser
"This analysis has identified a prognostic signature of three lncRNAs, namely LOC441179, PON2, and USP46-AS1, which could separate GBM samples with longer overall survival from those with shorter survival [ xref ]."

sparser
"Similarly, KAT2B , VWA1 , CX3CL1 , MLYCD , NR2F2 , USP46-AS1 , miR6724-4 , and LINC01257 were identified in the serum of chemo-nonresponsive patients as compared with responsive ones. xref KAT2B gene was one of the most dysregulated genes detected in RB specific sEV which corroborated with the treatment responsive RB. xref As part of further validation, we aimed to investigate the immunolocalization of EV markers alongside and Rb-specific markers in RB tissue."

sparser
"KAT2B , VWA1 , CX3CL1 , MLYCD , NR2F2 , USP46-AS1 , miR6724-4 , and LINC01257 genes were specifically dysregulated in TR-RB."

sparser
"Lower expression of FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 were associated with advanced tumor stage (Figure xref A); lower expression of RAP2C-AS1 was related to lymphatic invasion (Figure xref B); lower expression of RAP2C-AS1, USP46-AS1, AC112220.2 and AC015922.2 tended to promote tumor metastasis (Figure xref C); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 expression levels were correlated with higher pathological stage (Figure xref D); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2 and AC015922.2 expression levels were also correlated with higher histological grade (Figure xref E)."

sparser
"In this study, we found that several lncRNAs, including FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, ENSG00000271020, AC112220.2, AC018647.2, AC015922.2, MID1IP1-AS1, AL731577.2 and AL450326.1 were co-expressed with VHL, and their expression were positively correlated with VHL expression."

sparser
"In this study, we explored the association between ncRNA expression and glioma OS, and obtained a prognostic signature containing three ncRNAs, including USP46AS1 , PON2 and LOC441179 , based on which we could accurately separate glioma patients with better prognosis from those with a worse prognosis."
PHLPP1 affects USP46
13 | 7 10
PHLPP1 binds USP46.
13 | 6 10
13 | 4 10

sparser
"USP46 interacts with PHLPP in cells."

sparser
"Co-immunoprecipitation experiments showed that only USP46 specifically interacted with PHLPP1 in transfected 293T cells whereas other DUBs including USP7 and USP16 failed to binding PHLPP1, thus, demonstrating the specificity of USP46-mediated interaction ( xref )."

sparser
"Furthermore, the interaction between both endogenous PHLPP isoforms and USP46 was readily detected in DLD1 cells ( xref )."

No evidence text available

reach
"USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP in vitro and in cells."

sparser
"In CRC, a mutation in the protein WD repeat domain 48, required for interaction between PHLPP1 and USP12, resulted in PHLPP1 downregulation and consequent increase in AKT signaling ( Gangula and Maddi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"To determine if the interaction of PHLPP and USP46 is required for USP46-mediated increase of PHLPP expression, the full-length PHLPP1 or the USP46 binding-deficient Δ1139 mutant was co-expressed with USP46."

No evidence text available

No evidence text available

reach
"USP46 interacts with PHLPP in cells."
USP46 binds PHLPP1 and leucine. 1 / 1
| 1

reach
"Recently, a proteomic study on deubiquitinating enzymes and their associated protein complexes demonstrated that USP46 interacts with PHLPP and SCOP (PH-domain leucine rich repeat protein phosphatase and suprachiasmatic nucleus circadian oscillatory protein), which are members of the of Ser/Thr family of protein phosphatases XREF_BIBR."
USP46 binds PHLPP1 and 293T. 1 / 1
| 1

reach
"Co-immunoprecipitation experiments showed that only USP46 specifically interacted with PHLPP1 in transfected 293T cells whereas other DUBs including USP7 and USP16 failed to binding PHLPP1, thus, demonstrating the specificity of USP46 mediated interaction (XREF_FIG)."
PHLPP1 inhibits USP46.
| 1
PHLPP1 inhibits USP46. 1 / 1
| 1

reach
"The rate of cell proliferation followed the pattern of Akt phosphorylation that WT PHLPP1 was unable to significantly inhibit cell growth in USP46 knockdown cells (XREF_FIG)."

reach
"Some studies have shown that expression of USP46 is reduced in renal cell carcinoma (RCC), lung cancer and colon cancer and that USP46 suppresses cancer cell proliferation [ 24–26 ]."

reach
"CCK-8 and cell proliferation assays showed that overexpression of USP46 suppressed the proliferation capacity of Huh-7 cells ( Fig. 2 C and D)."

reach
"This result indicates that upregulation of USP46 inhibits tumor proliferation and growth.In contrast, we used two USP46-specific short hairpin RNA (shUSP46-1, shUSP46-2) plasmids to reduce USP46 expre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In summary, our results confirm that USP46 suppresses HCC proliferation and growth in vivo and in vitro ."

reach
"USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1 and AKT Pathway."

reach
"USP46 is downregulated in lung cancer and suppresses the proliferation of lung cancer cells by inhibiting the PHLPP1 and AKT pathway."

reach
"To determine if PHLPP and USP46 function together to negatively regulate cell proliferation, increasing amount of PHLPP1 plasmids was transfected into HCT116 cells alone or in combination with USP46."

reach
"We found that USP46 suppresses HCC cell proliferation, migration and invasion in vitro and metastasis in vivo , implying that USP46 may serve as a tumor suppressor in HCC."

reach
"However, tumor cells were resuspended in serum-free medium when we conducted invasion and migration assays, which showed that USP46 inhibits both the proliferation and invasion of HCC cells."

eidos
"In functional experiments , overexpression of USP46 impaired proliferation and metastasis of HCC cells , whereas knockdown of USP46 enhanced cell proliferation and invasiveness in vitro and in vivo ."

reach
"Consistently, the depletion of USP46 substantially inhibited cell proliferation of NRAS Q61R-transformed melanocytes in vitro and in vivo (Fig. 5b–d), whereas the depletion of USP46 in cells expressing FLAG-NRAS Q61R-2KR did not exert these effects (Supplementary Fig. 6a–d)."

reach
"AKT inhibition slows the proliferation of lung cancer cells that have been downregulated by USP46 and exposed to radiation."

reach
"As shown in Supplementary Fig. 6e, the depletion of USP46 in genetically engineered human immortalized melanocytes (hTERT/CDK4 /p53 ) expressing NRAS Q61R induced a significant reduction of cell proliferation as assessed by Ki67 staining, and a significant increase of apoptotic cell death as assessed by cleaved caspase-3 staining."

reach
"In functional investigations, USP46 knockdown increased cell proliferation and invasiveness in vitro and in vivo whereas overexpression of USP46 decreased HCC cell proliferation and metastasis."

reach
"As shown in Fig. 4 , overexpression of YAP1 enhanced HCC cell proliferation and invasion abilities, and re-expression of YAP1 attenuated the decrease in proliferation and invasion induced by overexpre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Collectively, our results indicated that miR-27a targets USP46 to promote EC cell proliferation and migration, suggesting an oncogene role of miR-27a in EC."

reach
"In contrast, a different study showed that USP46 promotes proliferation and tumor growth of HPV-transformed cancers [ 27 ]."
USP46 affects LRP6
| 22 5
USP46 increases the amount of LRP6.
| 8
USP46 increases the amount of LRP6. 8 / 8
| 8

reach
"We propose a model in which the USP46 complex increases the steady-state level of cell surface LRP6 and facilitates the assembly of LRP6 into signalosomes via a pruning mechanism that removes sterically hindering ubiquitin chains."

reach
"The USP46 complex acts upstream of the destruction complex to increase the steady-state levels of LRP6."

reach
"We observed that expression of the USP46 complex increased the cell-surface levels of LRP6 but not the insulin receptor control (Fig. 3F)."

reach
"The enzymatic activity of USP46 is required for Wnt activity as a catalytically inactive version of USP46, USP46 , did not increase LRP6 levels (Fig. 5A) or potentiate Wnt signaling in HEK293 STF cells (Supplementary Fig. 6A)."

reach
"Thus, the enzymatic activity of the USP46 complex is required for its regulation of LRP6 levels.We next examined if the USP46 complex increases LRP6 levels by promoting its deubiquitylation and opposing the activity of RNF43, an E3 ligase for Wnt receptors."

reach
"Similarly, we found that treatment with Bafilomycin A blocked the decrease in LRP6 levels following knockdown of USP46 in LF203 cells (Supplementary Fig. 6F)."

reach
"We found that knockdown of USP46 decreased the viability of intestinal organoids and LRP6 and β-catenin levels (Fig. 5F and Supplementary Fig. 7A, B) and that this effect was more evident at lower concentrations of RSPO (corresponds to higher RNF43/ZNRF3 activities)."

reach
"Knockdown of USP46 decreases steady-state levels of LRP6 and increases the level of ubiquitylated LRP6."
USP46 deubiquitinates LRP6.
| 8
USP46 deubiquitinates LRP6. 8 / 8
| 8

reach
"These results indicate that the USP46 complex promotes the deubiquitylation of LRP6 at the plasma membrane, thereby increasing its stabilization and opposing the action of the Wnt receptor ubiquitin ligases, RNF43 and ZNRF."

reach
"By reducing Arrow/LRP6 ubiquitylation, the Usp46 complex increases Arrow/LRP6 stability and cell surface levels, thereby enhancing the sensitivity of target cells to Wingless stimulation."

reach
"By reducing Arrow/LRP6 ubiquitylation and turnover and thus increasing cell surface Arrow levels, Usp46 enhances the sensitivity of target cells to Wingless stimulation."

reach
"The USP46 complex deubiquitylates LRP6 to promote Wnt/beta-catenin signaling."

reach
"Knockdown of USP46 decreases steady-state levels of LRP6 and increases the level of ubiquitylated LRP6."

reach
"Herein, we demonstrate that the USP46 complex is required for Wnt signaling in cultured human cells, Xenopus embryos, zebrafish embryos, and mouse intestinal organoids, indicating evolutionary conservation of function.We show that in response to Wnt pathway activation, the USP46 complex is recruited to and deubiquitylates cell surface LRP6, blocking its turnover."

reach
"USP46 inhibits the ubiquitylation of LRP6."

reach
"The USP46 complex blocks ubiquitylation/degradation of the Wnt co-receptor LRP6 [33]."
USP46 binds LRP6.
| 1 5
| 1 5

sparser
"Because the association of the USP46 complex with LRP6 was enhanced in the presence of Wnt stimulation (Fig.  xref ), we tested whether the USP46 complex interacted with LRP6 receptor aggregates in signalosomes that could be readily detected in sucrose density gradients xref ."

reach
"It remains to be determined whether the USP46 complex binds LRP6 as a pre-formed trimer or whether it proceeds through stepwise recruitment of individual subunits."

sparser
"It remains to be determined whether the USP46 complex binds LRP6 as a pre-formed trimer or whether it proceeds through stepwise recruitment of individual subunits."

sparser
"Wnt signaling promotes the binding of the USP46 complex to the Wnt coreceptor LRP6 at the cell surface, stabilizing LRP6 on the cell surface."

sparser
"The binding of the USP46 complex to LRP6 is enhanced by Wnt stimulation."

sparser
"Given its effect on LRP6 levels, we explored whether the USP46 complex interacted with LRP6."
USP46 activates LRP6.
| 3
USP46 activates LRP6. 3 / 3
| 3

reach
"These findings indicate that Arrow/LRP6 stabilization mediated by Usp46-dependent deubiquitylation is required for concentration-dependent responses in target cells, providing precision in signaling throughout the spatial range of the Wingless morphogen gradient."

reach
"These findings provide in vivo evidence that the Usp46 complex increases signaling strength by stabilizing Arrow/LRP6 and consequently promoting the cytoplasmic accumulation of Arm/β-catenin in Wingless-responding cells."

reach
"The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6."
USP46 ubiquitinates LRP6.
| 1
USP46 leads to the ubiquitination of LRP6. 1 / 1
| 1

reach
"By reducing Arrow/LRP6 ubiquitylation and turnover and thus increasing cell surface Arrow levels, Usp46 enhances the sensitivity of target cells to Wingless stimulation."
USP46 decreases the amount of LRP6.
| 1
USP46 decreases the amount of LRP6. 1 / 1
| 1

reach
"Knockdown of USP46 decreases steady-state levels of LRP6 and increases the level of ubiquitylated LRP6."
USP46 affects AKT
| 22 5
USP46 inhibits AKT.
| 6 2
USP46 inhibits AKT. 6 / 6
| 5 1

reach
"We thus conclude that the USP46 downregulated AKT pathway accounts for the inhibition of cell proliferation and migration in renal cell carcinoma, and USP46 functions as a tumor suppressor to repress [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"USP46 activates the Bcl-2 and caspase-3 apoptotic signaling pathway and inactivates AKT activity."

reach
"Functionally, USP46 mediated stabilization of PHLPP and the subsequent inhibition of Akt result in a decrease in cell proliferation and tumorigenesis of colon cancer cells in vivo."

sparser
"Verification of AKT inactivation by USP46 is also employed in different tumor scenarios."

reach
"Here, we show that USP46 and PHLPP function together to suppress Akt signaling in a mutually dependent manner."

reach
"Verification of AKT inactivation by USP46 is also employed in different tumor scenarios."
USP46 inhibits phosphorylated AKT. 2 / 2
| 1 1

reach
"Although USP46 was also upregulated in PD/SD tumors,, potential off-target effects of U4-I05 on USP46 were excluded, as U4-I05 treatment resulted in downregulation of p-AKT, which was inhibited by USP46 [35]."

sparser
"Although USP46 was also upregulated in PD/SD tumors,, potential off-target effects of U4-I05 on USP46 were excluded, as U4-I05 treatment resulted in downregulation of p-AKT, which was inhibited by USP46 [ xref ]."
USP46 activates AKT.
| 6
USP46 activates AKT. 6 / 6
| 6

reach
"USP46 mediated AKT inactivation is also used for verification in other tumor contexts."

reach
"Further studies are needed to investigate the regulation mechanism of USP46 mediated AKT inactivation and ascertain the functional effects of USP46 in RCC."

reach
"To determine the functional effects of USP46 in RCC and to further understand the regulatory mechanism of USP46-mediated AKT inactivation, more research is required."

reach
"Previous studies showed that USP46 functions as a tumor suppressor via PHLPP mediated AKT cascade inactivation in colon cancer."

reach
"AKT pathway downregulation caused by USP46 contributed to abnormalities in cell migration and proliferation."

reach
"Verification of AKT inactivation by USP46 is also employed in different tumor scenarios."
USP46 dephosphorylates AKT.
| 4 1
USP46 dephosphorylates AKT. 3 / 3
| 2 1

sparser
"Loss of USP46-induced upregulation of Akt dephosphorylation is similar as that observed by knocking down of PHLPP directly ( xref , xref )."

reach
"Deubiquitylase ovarian tumor deubiquitinase 1(OTUD1) and Ubiquitin-specific peptidase 46 (USP46) have been shown to decrease the phosphorylation of AKT at its N-terminus."

reach
"On the contrary, the depletion of USP46 markedly promoted AKT phosphorylation and S6K1 phosphorylation ( Fig. 4 B)."
USP46 leads to the dephosphorylation of AKT on T308. 1 / 1
| 1

reach
"As expected, USP46 overexpression decreased the phosphorylation of AKT in both the serine 473 and threonine 308 residues as well as the phosphorylation level of S6K1 ( Fig. 4 A)."
USP46 leads to the dephosphorylation of AKT on S473. 1 / 1
| 1

reach
"As expected, USP46 overexpression decreased the phosphorylation of AKT in both the serine 473 and threonine 308 residues as well as the phosphorylation level of S6K1 ( Fig. 4 A)."
USP46 phosphorylates AKT.
| 2 1
USP46 phosphorylates AKT. 3 / 3
| 2 1

reach
"Deubiquitylase ovarian tumor deubiquitinase 1(OTUD1) and Ubiquitin-specific peptidase 46 (USP46) have been shown to decrease the phosphorylation of AKT at its N-terminus."

reach
"In the present study, it was revealed that downregulation of USP46 expression levels could also promote the phosphorylation of AKT and mTOR, while the overexpression of USP46 could inhibit the phosphorylation levels."

sparser
"On the contrary, the depletion of USP46 markedly promoted AKT phosphorylation and S6K1 phosphorylation ( Fig. 4 B)."
USP46 increases the amount of AKT.
| 2
USP46 increases the amount of phosphorylated AKT. 2 / 2
| 2

reach
"As shown in Fig. 7j and Supplementary Fig. 10g, the overexpression of USP46 WT, but not the 3 A mutant in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly increased the protein level of NRAS mutants and levels of p-AKT and p-ERK."

reach
"Furthermore, the depletion of USP46 in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly suppressed levels of p-AKT and p-ERK, cellular proliferation, migration and invasion abilities along with increased cellular sensitivity to DTIC, whereas the reconstitution of NRAS Q61R/K, NRAS Q61R-K135R + K147R or NRAS Q61R-K135R + K147L in USP46-deficient cells markedly rescue such effects (Fig. 5i–l and Supplementary Figs."
USP46 decreases the amount of AKT.
| 2
USP46 decreases the amount of phosphorylated AKT. 1 / 1
| 1

reach
"USP46 is known to downregulate p-AKT expression [35]."
USP46 decreases the amount of AKT. 1 / 1
| 1

reach
"USP46 decreases the phosphorylation levels of AKT to inhibit cell proliferation and migration in RCC cells (Gui et al., 2019)."
USP46 binds AKT.
| 1
| 1

sparser
"As previously described, USP46 mediated PHLPP stability in colon cancer through AKT inaction, indicating a novel mechanism of the USP46-AKT axis in tumor regulation."
USP46 affects NRAS
| 17 6
USP46 binds NRAS.
| 1 6
| 6

sparser
"Similarly, the interaction of USP46 and NRAS Q61R is much stronger than NRAS WT pretreated with GDP or GTPγS (Fig. xref )."

sparser
"The direct interaction of USP46 and NRAS mutants prompt us to examine whether USP46 is essential to regulate the stability and oncogenic function of NRAS mutants."

sparser
"In our study, the interaction of USP46 with NRAS WT and Q61L mutant is weaker than NRAS Q61R or Q61K (Fig. xref ), which might be due to the conformation difference and charge alterations between the positively charged mutations (Q61R and Q61K) and non-polar mutation (Q61L)."

sparser
"The endogenous interaction between USP46 and NRAS Q61R was validated in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells, respectively (Fig. xref and Supplementary Fig.  xref )."

sparser
"We also examined the interaction between purified USP46 and different NRAS mutants."

sparser
"The basic amino acids K61 and R61 could form a salt bridge with the acidic residue E333 of USP46, thereby enhancing the interaction between USP46 and NRAS Q61K/R mutants."
USP46 binds NRAS-Q61R. 1 / 1
| 1

reach
"The endogenous interaction between USP46 and NRAS Q61R was validated in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells, respectively (Fig. 3c, d and Supplementary Fig. 3a)."
USP46 increases the amount of NRAS.
| 5
USP46 increases the amount of mutated NRAS. 4 / 4
| 4

reach
"We found that the knockdown of USP46 in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly decreased the protein level of NRAS mutants (Fig. 4a and Supplementary Fig. 4a)."

reach
"In addition, the overexpression of USP46 WT in SK-MEL-103 and SK-MEL-30 cells significantly increased the protein level of NRAS mutants, which could be largely mitigated by the treatment of PF670462 (Fig. 7c and Supplementary Fig. 10a)."

reach
"As shown in Fig. 7j and Supplementary Fig. 10g, the overexpression of USP46 WT, but not the 3 A mutant in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly increased the protein level of NRAS mutants and levels of p-AKT and p-ERK."

reach
"Compared to control cells (shScramble), the depletion of USP46 in SK-MEL-103 cells expressing FLAG-NRAS Q61R markedly decreased the protein level of the NRAS mutant, inhibited the activation of downstream pathways assessed by p-AKT and p-ERK, reduced cell proliferation, and increased cellular sensitivity to DTIC."
USP46 increases the amount of NRAS. 1 / 1
| 1

reach
"As shown in Fig. 5a, the depletion of USP46 in genetically engineered human immortalized melanocytes (hTERT/CDK4 /p53 ) expressing NRAS Q61R significantly decreased the protein level of NRAS and suppressed the activation of downstream pathways assessed by p-AKT and p-ERK."
USP46 decreases the amount of NRAS.
| 5
USP46 decreases the amount of NRAS-Q61R. 3 / 3
| 3

reach
"In addition, the reduced protein level of NRAS Q61R in USP46-deficient SK-MEL-103 cells could be largely rescued by the reconstitution of USP46 WT, but not the 3 A mutant (Fig. 7h)."

reach
"Conversely, the depletion of USP46 in SK-MEL-103 cells markedly increased the ubiquitination level of NRAS Q61R (Fig. 4j)."

reach
"Consistently, the overexpression of USP46 WT dramatically decreased the ubiquitination level of NRAS Q61R, which was markedly abrogated by the depletion or inhibition of CK1δ by PF670462 or Casein kinase 1δ-IN-8 rather than β-catenin inhibitor MSAB (Fig. 7d, e and Supplementary Fig. 10f)."
USP46 decreases the amount of NRAS. 1 / 1
| 1

reach
"And USP46 WT but not its catalytically inactive mutant C44S dramatically decreased the ubiquitination level of NRAS Q61R/K (Fig. 4f–h)."
USP46 decreases the amount of mutated NRAS. 1 / 1
| 1

reach
"As shown in Fig. 7f, g, the overexpression of USP46 WT could dramatically decrease the ubiquitination level of NRAS mutants, whereas the 3 A mutant failed to do so."
USP46 activates NRAS.
| 3
USP46 activates mutated NRAS. 1 / 1
| 1

reach
"Moreover, the reconstitution of USP46 WT in endogenous USP46-deficient SK-MEL-103 cells dramatically increased the half-life of NRAS mutant compared to the 3 A mutant (Fig. 7i)."
USP46 activates NRAS. 1 / 1
| 1

reach
"We next investigate whether USP46 promotes tumorigenesis and progression of melanoma harboring NRAS Q61R/K mutants."
USP46 activates NRAS-Q61R. 1 / 1
| 1

reach
"Consistently, the depletion of USP46 substantially inhibited cell proliferation of NRAS Q61R-transformed melanocytes in vitro and in vivo (Fig. 5b–d), whereas the depletion of USP46 in cells expressing FLAG-NRAS Q61R-2KR did not exert these effects (Supplementary Fig. 6a–d)."
USP46 deubiquitinates NRAS.
| 2
USP46 leads to the deubiquitination of mutated NRAS. 1 / 1
| 1

reach
"USP46 deubiquitinates and stabilizes oncogenic NRAS mutants."
USP46 deubiquitinates NRAS. 1 / 1
| 1

reach
"Together, these results indicate that USP46 specifically deubiquitinates and stabilizes NRAS Q61R/K mutants in melanoma but not NRAS WT, KRAS WT, HRAS WT and their mutants.We next examined the specific ubiquitin linkage of NRAS mutants cleaved by USP46."
USP46 ubiquitinates NRAS.
| 1
USP46 ubiquitinates NRAS. 1 / 1
| 1

reach
"As shown in Supplementary Fig. 4h, i, the protein level of NRAS WT was not significantly affected by the depletion of USP46 in A375 and A2058, two melanoma cell lines harboring NRAS WT, since USP46 WT failed to affect the ubiquitination of NRAS WT."
USP46 is modified
| 23
USP46 is phosphorylated.
| 21
USP46 is phosphorylated. 10 / 15
| 15

sparser
"As the phosphorylation of USP46 is poorly studied, the protein kinases other than CK1δ responsible for the basic phosphorylation of USP46 need further investigation in the future."

sparser
"CK1δ-mediated phosphorylation of USP46 in the in vitro kinase assay was detected by using phospho-tag gel, which was significantly mitigated by the treatment of PF670462 (Fig. xref )."

sparser
"The single mutation of USP46 T209A, S351A or S354A only mildly decreased the phosphorylation of USP46, while the 3A mutant (T209A/S351A/S354A) almost completely abolished it assessed by phospho-tag gel (Fig. xref )."

sparser
"Mechanistically, CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity towards NRAS mutants, thus promoting oncogenic NRAS-driven melanocyte malignant transformation and melanoma progression in vitro and in vivo."

sparser
"Furthermore, the in vitro kinase assay was performed by using anti-p-Ser and anti-p-Thr antibodies to examine the phosphorylation of USP46 isolated from SK-MEL-103 cells stably expressing pLVX3-GST-USP46 WT and the 3A mutant."

sparser
"Mechanistically, CK1δ directly phosphorylates and activates USP46, thereby promoting oncogenic NRAS-driven melanocyte transformation and tumor progression."

sparser
"As shown in Supplementary Fig.  xref , CK1δ significantly increased the phosphorylation of USP46 WT assessed by anti-p-Ser and anti-p-Thr antibodies, whereas the 3A mutant could largely decrease such phosphorylation events."

sparser
"Intriguingly, some basal phosphorylation of isolated USP46 from SK-MEL-103 cells was noticed even in the absence of CK1δ, indicating that other protein kinases might also contribute to the phosphorylation of USP46."

sparser
"CK1δ-mediated phosphorylation of USP46 regulates tumor progression of oncogenic NRAS-driven melanoma."

sparser
"Next, we examined the effect of CK1δ-mediated phosphorylation of USP46 on the ubiquitination of NRAS mutants."
USP46 is phosphorylated on S354. 2 / 2
| 2

sparser
"This result suggests that CK1δ could regulate the phosphorylation of USP46 at Thr209, Ser351 and Ser354 residues, which all contain the S/T-X-X-S/T motif."

sparser
"CK1δ binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."
USP46 is phosphorylated on S351. 2 / 2
| 2

sparser
"This result suggests that CK1δ could regulate the phosphorylation of USP46 at Thr209, Ser351 and Ser354 residues, which all contain the S/T-X-X-S/T motif."

sparser
"CK1δ binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."
USP46 is phosphorylated on T209. 2 / 2
| 2

sparser
"This result suggests that CK1δ could regulate the phosphorylation of USP46 at Thr209, Ser351 and Ser354 residues, which all contain the S/T-X-X-S/T motif."

sparser
"CK1δ binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."
USP46 is ubiquitinated.
| 2
USP46 is ubiquitinated. 2 / 2
| 2

sparser
"Specifically, ubiquitination of PSD-95 ( xref ) and the deubiquitinating enzyme USP46 ( xref ) regulate AMPA receptors at the synapse."

sparser
"The increase in USP46 expression following Depdc5 deletion is supported by the observation that USP46 is ubiquitinated, and the association with WDR48 stabilizes USP46 by preventing its ubiquitination and successive degradation in the proteasome ( xref )."
USP46 affects STK4
2 | 15 5
USP46 binds STK4.
2 | 2 5
2 | 2 5

sparser
"In conclusion, we found that USP46 interacts with MST1 and decreases the polyubiquitination of MST1, stabilizing MST1 and leading to the inactivation of YAP1 in HCC."

sparser
"To test this hypothesis, we first validated the specificities of USP46 and MST1 interactions in HCC cells."

No evidence text available

sparser
"As expected, co-IP assays confirmed the interaction between USP46 and MST1 using endogenous USP46 and MST1 antibodies in Huh-7 and Hep3B cells ( Fig. 6 A)."

No evidence text available

sparser
"In addition, we revealed that USP46 interacts with the Hippo pathway core component MST1."

reach
"To test this hypothesis, we first validated the specificities of USP46 and MST1 interactions in HCC cells."

reach
"As expected, co-IP assays confirmed the interaction between USP46 and MST1 using endogenous USP46 and MST1 antibodies in Huh-7 and Hep3B cells ( Fig. 6 A)."

sparser
"Furthermore, USP46 directly binds to the MST1 protein and lowers its ubiquitination, stabilizing it."
USP46 increases the amount of STK4.
| 5
USP46 increases the amount of STK4. 5 / 5
| 5

reach
"As a deubiquitinating enzyme, USP46 is responsible for the process of protein deubiquitination, and we hypothesized that USP46 mediated the upregulation of MST1 by modulating the ubiquitination level [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Scientifically, USP46 stimulates MST1 expression, which in turn antagonizes YAP1 to inhibit the development of HCC by promoting the breakdown of YAP1."

reach
"Overexpression of USP46 increased protein expression of MST1, phosphorylated MST1 and phosphorylated LATS1 ( Fig. 5 B)."

reach
"In addition, overexpression of USP46 increased ectopic expression of MST1 in a dose-dependent manner ( Fig. 6 E)."

reach
"Our results indicate that the regulatory axis by which USP46 promotes the degradation of YAP1 by upregulating MST1 expression also exists in HCC tissues.As a deubiquitinating enzyme, USP46 is involved[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 decreases the amount of STK4.
| 3
USP46 decreases the amount of STK4. 3 / 3
| 3

reach
"Third, USP46 silencing increased ubiquitination levels of MST1, whereas overexpression of USP46 decreased levels of MST1 ubiquitination.In conclusion, we found that USP46 interacts with MST1 and decre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Finally, ectopic expression of USP46 inhibited the ubiquitination level of MST1, whereas knockdown of USP46 increased the polyubiquitination of MST1 ( Fig. 6 G and H)."

reach
"Therefore, we speculated that USP46 suppressed YAP1 by regulating MST1 protein expression in HCC."
USP46 deubiquitinates STK4.
| 2
USP46 leads to the deubiquitination of STK4. 2 / 2
| 2

reach
"Third, USP46 silencing increased ubiquitination levels of MST1, whereas overexpression of USP46 decreased levels of MST1 ubiquitination.In conclusion, we found that USP46 interacts with MST1 and decre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In summary, our results demonstrated that USP46 inhibits ubiquitination of MST1 via its deubiquitination function, stabilizing the MST1 protein.To verify whether the above regulatory axis also exists [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 activates STK4.
| 2
USP46 activates STK4. 2 / 2
| 2

reach
"USP46 may promote degradation of YAP1 by stabilizing MST1 but not LATS1."

reach
"First, USP46 prolongs the half-life of MST1."
USP46 inhibits STK4.
| 1
USP46 inhibits STK4. 1 / 1
| 1

reach
"As shown in Fig. 6 C and D, the increase in USP46 significantly inhibited degeneration of MST1 protein in HCC cells."
USP46 affects GLR1.1
| 17 2
USP46 activates GLR1.1.
| 6
USP46 activates GLR1.1. 5 / 5
| 5

reach
"Taken together with our previous data, these results suggest that USP-46 prevents the degradation of GLR-1 and promotes its surface expression in the VNC."

reach
"This result suggests that the deubiquitinating activity of USP-46 is required in glr-1-expressing interneurons to promote GLR-1 abundance."

reach
"Furthermore, the co-localization of mCherry : : USP-46 and the endosomal marker Venus : : RAB-5 in the cell body and VNC (XREF_SUPPLEMENTARY) support a model in which USP-46 functions at an endosomal compartment to prevent the targeting of GLR-1 for degradation."

reach
"These data suggest a model whereby USP-46 promotes the abundance of GLR-1 at synapses by acting in a pre-MVB compartment (i.e. endosome) to deubiquitinate GLR-1 and thus prevent its lysosomal degradation (XREF_FIG)."

reach
"Several lines of evidence indicate that USP-46 negatively regulates GLR-1 degradation by deubiquitinating the receptor."
Mutated USP46 activates ubiquitinated GLR1.1. 1 / 1
| 1

reach
"Conversely, mutant USP46 increases ubiquitinated GLR-1."
USP46 deubiquitinates GLR1.1.
| 5
USP46 deubiquitinates GLR1.1. 5 / 5
| 5

reach
"These data support a model in which USP-46 promotes GLR-1 abundance at synapses by deubiquitinating GLR-1 and preventing its degradation in the lysosome."

reach
"These data demonstrate that USP-46 promotes the deubiquitination of GLR-1, which in turn increases the abundance of GLR-1 in the VNC."

reach
"These findings suggest that USP-46 functions to deubiquitinate GLR-1 and to protect the receptor from degradation."

reach
"The abundance of GLR-1 (4KR), a mutant receptor which can not be ubiquitinated, is unaffected in usp-46 loss-of-function mutants leading to a model where USP-46 deubiquitinates GLR-1 to regulate its abundance."

reach
"Second, we tested whether the amount of ubiquitinated GLR-1 is increased in usp-46 mutant animals, as would be expected if USP-46 deubiquitinates GLR-1."
USP46 binds GLR1.1.
| 3 2
| 2 2

reach
"First, we tested whether USP-46 could interact with GLR-1, as might be expected if GLR-1 were a deubiquitination target of USP-46."

sparser
"Biochemical results indicate that although bacterially-expressed recombinant USP46 can interact with GLR-1 from worm extracts, it only exhibits a low level of DUB activity [ xref ]."

sparser
"In the ventral nerve cord of C. elegans it was found that USP46 binds to GLR-1, and negatively regulates the levels of its ubiquitination."

reach
"In the ventral nerve cord of C. elegans it was found that USP46 binds to GLR-1, and negatively regulates the levels of its ubiquitination."
USP46 binds ubiquitinated GLR1.1. 1 / 1
| 1

reach
"Since recombinant GST-GLR-1C is not ubiquitinated, these data are consistent with the idea that USP-46 binds to ubiquitinated GLR-1, which has previously been shown to make up less than 0.5% of total GLR-1 in worms."
USP46 increases the amount of GLR1.1.
| 2
USP46 bound to WDR48 increases the amount of GLR1.1. 1 / 1
| 1

reach
"Mechanistically, USP46 can bind with WD40-repeat (WDR) proteins WDR-20 and WDR-48 to stimulate USP46 catalytic activity and increase GLR-1 levels."
USP46 bound to WDR20 increases the amount of GLR1.1. 1 / 1
| 1

reach
"Mechanistically, USP46 can bind with WD40-repeat (WDR) proteins WDR-20 and WDR-48 to stimulate USP46 catalytic activity and increase GLR-1 levels."
USP46 decreases the amount of GLR1.1.
| 1
USP46 decreases the amount of ubiquitinated GLR1.1. 1 / 1
| 1

reach
"Taken together, these data indicate that USP-46 negatively regulates the amount of ubiquitinated GLR-1 in vivo."
USP46 affects methane
| 18
USP46 deubiquitinates methane.
| 6
USP46 deubiquitinates methane. 6 / 6
| 6

reach
"By reducing Arrow ubiquitylation and turnover, the Usp46 complex increases cell surface levels of Arrow and enhances the sensitivity of target cells to stimulation by the Wingless morphogen, thereby increasing the amplitude and spatial range of signaling responses."

reach
"By reducing Arrow/LRP6 ubiquitylation, the Usp46 complex increases Arrow/LRP6 stability and cell surface levels, thereby enhancing the sensitivity of target cells to Wingless stimulation."

reach
"We found that the Usp46 complex markedly decreased levels of ubiquitylated Arrow (Fig. 8A)."

reach
"Similarly, the Usp46 complex decreased endogenous levels of ubiquitylated Arrow in S2R+ cells (Fig. 8B)."

reach
"These results provide evidence that Arrow deubiquitylation by the Usp46 complex increases Arrow levels at the cell surface and thereby promotes Wingless signaling (Fig. 8D)."

reach
"By reducing Arrow/LRP6 ubiquitylation and turnover and thus increasing cell surface Arrow levels, Usp46 enhances the sensitivity of target cells to Wingless stimulation."
USP46 increases the amount of methane.
| 4
USP46 increases the amount of methane. 4 / 4
| 4

reach
"These findings revealed that the Usp46 complex increased Arrow levels at the cell surface (Fig. 8C)."

reach
"These results provide evidence that Arrow deubiquitylation by the Usp46 complex increases Arrow levels at the cell surface and thereby promotes Wingless signaling (Fig. 8D)."

reach
"By reducing Arrow/LRP6 ubiquitylation and turnover and thus increasing cell surface Arrow levels, Usp46 enhances the sensitivity of target cells to Wingless stimulation."

reach
"By reducing Arrow ubiquitylation and turnover, the Usp46 complex increases cell surface levels of Arrow and enhances the sensitivity of target cells to stimulation by the Wingless morphogen, thereby increasing the amplitude and spatial range of signaling responses."
USP46 activates methane.
| 3
USP46 activates methane. 3 / 3
| 3

reach
"The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6."

reach
"These findings provide in vivo evidence that the Usp46 complex increases signaling strength by stabilizing Arrow/LRP6 and consequently promoting the cytoplasmic accumulation of Arm/β-catenin in Wingless-responding cells."

reach
"Finally, to test if the Usp46 complex promotes the deubiquitylation and resultant stabilization of the plasma membrane pool of endogenous Arrow, we performed cell surface biotinylation of S2R+ cells."
USP46 ubiquitinates methane.
| 2
USP46 leads to the ubiquitination of methane. 2 / 2
| 2

reach
"By reducing Arrow/LRP6 ubiquitylation and turnover and thus increasing cell surface Arrow levels, Usp46 enhances the sensitivity of target cells to Wingless stimulation."

reach
"By reducing Arrow ubiquitylation and turnover, the Usp46 complex increases cell surface levels of Arrow and enhances the sensitivity of target cells to stimulation by the Wingless morphogen, thereby increasing the amplitude and spatial range of signaling responses."
USP46 decreases the amount of methane.
| 2
USP46 decreases the amount of methane. 2 / 2
| 2

reach
"Similarly, the Usp46 complex decreased endogenous levels of ubiquitylated Arrow in S2R+ cells (Fig. 8B)."

reach
"We found that the Usp46 complex markedly decreased levels of ubiquitylated Arrow (Fig. 8A)."
USP46 inhibits methane.
| 1
| 1

reach
"Similarly, when driven by the C96-Gal4 driver, the Arrow overexpression phenotype was rescued by depletion of either Usp46 or Wdr20 (Fig. S21)."
| 1 17
| 10

reach
"In functional investigations, USP46 knockdown increased cell proliferation and invasiveness in vitro and in vivo whereas overexpression of USP46 decreased HCC cell proliferation and metastasis."

reach
"These results indicated that USP46 promotes ESCC cell metastasis through regulating ENO1.To further validate the relationship of USP46 and ENO1 in ESCC, we examined the expression of ENO1 in 48 clinic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Besides, USP46 promotes ESCC metastasis by regulating EMT process and has an effect of inhibiting ubiquitination of ENO1 protein."

reach
"Functionally, USP46 promotes ESCC metastasis in vitro and in vivo by inducing the EMT process."

reach
"Our studies illustrated that USP46 could strikingly promote cell migration, invasion and tumor metastasis of ESCC."

reach
"However, we noticed that USP46 is a contributor of ESCC tumor metastasis in vitro and in vivo ."

reach
"Moreover, knockdown USP46 particularly suppressed mobility of ESCC cells and tumor metastasis in vitro and in vivo ."

reach
"These results implicated that USP46 promotes ESCC tumor metastasis in a catalytic-dependent way."

reach
"Collectively, these results displayed that USP46 enhances the metastatic capacity of ESCC cells through inducing the process of EMT in a catalytic-dependent way.Given that USP46 promotes ESCC cell met[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In addition to affecting the proliferation of cancer cells, USP46 has also been demonstrated to promote tumor metastasis by stabilizing ENO1 in human esophageal squamous cell carcinoma [ 28 ]."
| 1 7

reach
"Furthermore, our results demonstrated that USP46 suppresses HCC proliferation and metastasis by inhibiting the MST1/YAP1 axis."

reach
"These experimental results indicate that USP46 inhibits the invasion and metastasis of hepatoma cells in vivo and in vitro ."

eidos
"Furthermore , we found that USP46 suppresses HCC cell proliferation and metastasis by inhibiting YAP1 ."

reach
"There are several lines of experimental evidence suggesting that USP46 inhibits cancer cell proliferation and metastasis."

reach
"In functional investigations, USP46 knockdown increased cell proliferation and invasiveness in vitro and in vivo whereas overexpression of USP46 decreased HCC cell proliferation and metastasis."

reach
"Indeed, USP46 inhibition significantly increased YAP1, as well as the proliferation and metastasis of HCC cells."

reach
"In addition, USP46 functions as an MST1 DUB, enhancing MST1 kinase activity to inhibit tumor development and metastasis."

reach
"We found that USP46 suppresses HCC cell proliferation, migration and invasion in vitro and metastasis in vivo , implying that USP46 may serve as a tumor suppressor in HCC."
USP46 affects DTL
| 2 15
USP46 binds DTL.
| 15
| 10

sparser
"E6 protein promotes the interaction of USP46 with Cdt2."

sparser
"Thus there was a perfect correlation between an E6 variant’s ability to bind USP46 and promote the interaction of USP46 with Cdt2, and the ability of the variant to stabilize Cdt2."

sparser
"Concurrently, E6 forms a complex with the deubiquitinating enzyme USP46 in cervical cancer cells, promoting interaction between USP46 and Cdt2 (a component of the CRL4 Cdt2 E3 ubiquitin ligase complex)."

sparser
"Therefore although our co-immunoprecipitation experiments showed that DDB1 is present in the USP46:Cdt2 complex [ xref ], neither DDB1 nor a substrate of the CRL4-Cdt2 complex is required for the E6:USP46:Cdt2 interaction and subsequent Cdt2 stabilization"

sparser
"Immunoprecipitation of endogenous cellular Cdt2 coimmunoprecipitated cellular USP46 and E6 only from HeLa cell lysates (that contain HPV E6) but not from U2OS cell lysates (that do not contain E6) ( xref ; xref ), suggesting that E6 is necessary to promote the interaction of Cdt2 with USP46."

sparser
"In contrast, Flag-Cdt2 alone from cells without E6 did not co-immunoprecipitate endogenous USP46 ( xref , lane 1), suggesting that Cdt2 and USP46 do not interact with each other in the absence of E6."

sparser
"Thus, HPV E6 binds directly to USP46, and this facilitates the interaction of USP46 with its potential substrate Cdt2."

sparser
"Only high risk but not low risk E6 proteins could promote Cdt2 interaction with USP46 and stabilize Cdt2."

sparser
"If the interaction of USP46 with Cdt2 is essential for the stabilization of Cdt2, we would expect that the residues of E6 required to stabilize Cdt2 are also essential to promote the interaction of USP46 with Cdt2."

sparser
"Immunoprecipitation of Cdt2 and immunoblotting of the precipitate for USP46 showed that high risk 16E6 and the 1–43 fragment of 16E6, but not low risk 6E6 or 16E6-F2V/P5R, promoted the interaction of USP46 and Cdt2 ( xref ), demonstrating the correlation expected above."
E6 binds USP46 and DTL. 3 / 3
| 3

sparser
"The elution profile also suggests that the Cdt2 associates with E6-USP46, as a low-affinity substoichiometric substrate rather than as a core member of the E6-USP46 complex."

sparser
"In Hela cells, E6 is associates with E6AP and p53, and now we find that the E6 protein also associates with USP46 and Cdt2."

sparser
"We propose that the E6-USP46 interaction promotes the tripartite E6-USP46-Cdt2 complex either due to allosteric changes in USP46, or because Cdt2 interacts simultaneously with sites on E6 and USP46 ( xref )."
USP6 binds USP46 and DTL. 1 / 1
| 1

sparser
"Moreover, miR-3680-5p was associated with the USP6 , USP32 , USP46 , and DTL genes, which have roles in the ubiquitin (deubiquitin) proteolysis system."
USP46 binds DTL and IL17RB. 1 / 1
| 1

sparser
"Immunoprecipitates of myc-USP46 contained Cdt2 and DDB1 indicating that USP46 associates with CRL4-Cdt2 complex ( xref )."
USP46 deubiquitinates DTL.
| 2
USP46 deubiquitinates DTL. 2 / 2
| 2

reach
"Then, USP46 deubiquitinates Cdt2 leading to continuous regulation of the CRL4 Cdt2 substrates and cell cycle deregulation [ 10 ] ( Figure 3 A)."

reach
"It has been shown earlier in HR HPV cancer cells that E6 protein protects Cdt2 from ubiquitin-mediated degradation by recruiting a deubiquitinase, USP46 to deubiquitinate and stabilise Cdt2, which is essential for proliferation and survival of these cells [14]."
USP46 affects GRIA1
1 1 | 14
USP46 deubiquitinates GRIA1.
1 | 4
USP46 deubiquitinates GRIA1. 5 / 5
1 | 4

reach
"In a similar manner to USP8, the reduction in USP46 through knockdown enhances basal GluA1 ubiquitination while diminishing its neuronal expression [177]."

"This Editorial Highlight discusses the relevance of a study published in the current issue of Journal of Neurochemistry, in which the authors Huo and collaborators now identified ubiquitin-specific peptidase 46 (<span class="match term0">USP46</span>) as a specific AMPAR deubiquitinase."

reach
"Mammalian USP46 can deubiquitinate both GluA1 and GluA2 subunits and protect AMPARs from degradation."

reach
"Similarly, overexpression of USP46 downregulates the ubiquitination of GluA1 and reduces the accumulation of internalized GluA1 in neurons [177]; therefore, it has been suggested that ubiquitination of AMPARs is necessary for internalization and thus occurs prior."

reach
"We observed that USP46 is able to deubiquitinate not only GluA1 but also GluA2, indicating a relative stringency in contrast to the distinct E3 ligases that are employed for GluA1 and GluA2."
USP46 inhibits GRIA1.
| 3
USP46 inhibits GRIA1. 3 / 3
| 3

reach
"Internalized GluA1 puncta density was also significantly reduced by USP46 over-expression (XREF_FIG) (Control : 6.42 +/- 0.40 puncta per 10 mum, n = 12 neurons; USP46 : 4.73 +/- 0.61 puncta per 10 mum, n = 12 neurons, p = 0.03)."

reach
"Similarly, overexpression of USP46 downregulates the ubiquitination of GluA1 and reduces the accumulation of internalized GluA1 in neurons [177]; therefore, it has been suggested that ubiquitination of AMPARs is necessary for internalization and thus occurs prior."

reach
"We showed that in HEK cells USP46 over-expression negatively regulates the turnover rate of GluA1 and thus stabilizes GluA1 from degradation."
USP46 ubiquitinates GRIA1.
| 2
USP46 ubiquitinates GRIA1. 2 / 2
| 2

reach
"These include : (a) overexpression of Nedd4-1 in neurons, which enhances GluA1 ubiquitination, causes a reduction in the number of AMPARs on the plasma membrane; (b) shRNA mediated knockdown of Nedd4-1 increases the rate of GluA1 internalization; (c) overexpression of USP46, which downregulates GluA1 ubiquitination, decreases the accumulation of internalized GluA1 in neurons; and (d) overexpression of GluA1-4KR ubiquitin deficient mutants (where all four C-terminal lysine residues have been substituted with arginines) blocks AMPA induced GluA1 internalization."

reach
"By deubiquitinating K63 ubiquitinated glutaminergic AMPARs (α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid) receptors GluA1 and GluA2, which are considered to mediate most of the excitatory synaptic transmission in the brain, USP46 upregulates the intracellular trafficking, cell surface density, and signal intensity of AMPARs [116,117]."
USP46 increases the amount of GRIA1.
| 2
USP46 increases the amount of ubiquitinated GRIA1. 1 / 1
| 1

reach
"Decreased mEPSC amplitudes, lower surface, and total levels of GluA1, and higher amounts of ubiquitinated GluA1 are the outcomes of USP46 knockdown, which is consistent with USP46’s function in deubiquitinating mammalian AMPARs."
USP46 increases the amount of GRIA1. 1 / 1
| 1

reach
"Decreased mEPSC amplitudes, lower surface, and total levels of GluA1, and higher amounts of ubiquitinated GluA1 are the outcomes of USP46 knockdown, which is consistent with USP46’s function in deubiquitinating mammalian AMPARs."
USP46 activates GRIA1.
| 2
USP46 activates GRIA1. 2 / 2
| 2

reach
"Recently, invivo and invitro studies demonstrated that the DUB USP46 also targets GluA1, regulating AMPAR surface expression, endocytosis, and the strength of synaptic transmission (Huo etal."

reach
"We found that the surface GluA1 was significantly enhanced by USP46 over-expression."
USP46 decreases the amount of GRIA1.
| 1
Modified USP46 decreases the amount of GRIA1. 1 / 1
| 1

reach
"In infected cortical neurons, over-expression of USP46 significantly reduced the ubiquitination level of GluA1, whereas over-expression of USP12 showed no effect (XREF_FIG), again indicating the specificity of USP46 toward GluA1."
USP46 binds GRIA1.
1 |
1 |

No evidence text available
USP46 affects GRIA
| 15 1
USP46 deubiquitinates GRIA.
| 9
USP46 deubiquitinates GRIA. 9 / 9
| 9

reach
"USP46, which is known to be enriched at the neural synapse, may modulate brain function by deubiquitinating AMPAR."

reach
"Ubiquitin-specific protease 46 (USP46) deubiquitinates the glutamate receptors GLR-1 and AMPAR, resulting in increased surface levels of these receptors [149, 150]."

reach
"In AD brains and neurons incubated with Aβ, USP46 expression is downregulated, triggering ubiquitination, and clearance of AMPARs."

reach
"They discovered that K63-type ubiquitination affects AMPARs and that both in vivo and in vitro, USP46 can deubiquitinate AMPARs."

reach
"All of these findings point to a conserved mechanism in which USP46 deubiquitinates AMPARs at synapses to prevent their breakdown and to encourage their recycling to the cell surface, which in turn impacts synapse function."

reach
"Given the same type of deubiquitinating enzyme (USP46) is able to deubiquitinate AMPA receptors, and knockdown of USP46 elevated AMPA receptor ubiquitination and reduced AMPA receptor expression in hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Endogenous USP46 suppresses AMPAR ubiquitination in neurons."

reach
"We found that USP46 suppressed AMPAR ubiquitination leading to an increase in receptor protein amount as well as in receptor synaptic localization."

reach
"USP46 over-expression leads to a reduction in AMPAR ubiquitination, whereas knockdown of USP46 by either siRNAs or shRNAs causes a significant increase in AMPAR ubiquitination."
USP46 ubiquitinates GRIA.
| 2 1
USP46 leads to the ubiquitination of GRIA. 3 / 3
| 2 1

sparser
"Given the same type of deubiquitinating enzyme (USP46) is able to deubiquitinate AMPA receptors, and knockdown of USP46 elevated AMPA receptor ubiquitination and reduced AMPA receptor expression in hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In AD brains and neurons incubated with Aβ, USP46 expression is downregulated, triggering ubiquitination, and clearance of AMPARs."

reach
"Expression of USP46 causes AMPAR ubiquitination in heterologous cells and neurons to significantly decrease, along with AMPAR decomposition rate diminution and surface AMPAR accumulation increase."
USP46 activates GRIA.
| 2
USP46 activates GRIA. 2 / 2
| 2

reach
"In contrast, RNA interference (RNAi)-mediated knockdown of USP46 results in increased AMPAR ubiquitination and decreased surface AMPARs at neuronal synapses."

reach
"These functions of CYLD were implied in a study on another K63-DUB, USP46, which can cleave K63-linked ubiquitination chains from AMPARs and modulate AMPAR internalization and turnover in cultured rat cortical and hippocampal neurons; in this way, USP46 is thought to regulate AMPAR-mediated excitatory synaptic transmission (Huo et al., 2015)."
USP46 inhibits GRIA.
| 1
USP46 inhibits GRIA. 1 / 1
| 1

reach
"USP46 over-expression suppresses AMPAR internalization."
USP46 decreases the amount of GRIA.
| 1
USP46 decreases the amount of GRIA. 1 / 1
| 1

reach
"Given the same type of deubiquitinating enzyme (USP46) is able to deubiquitinate AMPA receptors, and knockdown of USP46 elevated AMPA receptor ubiquitination and reduced AMPA receptor expression in hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects YAP1
| 1 12 2
USP46 inhibits YAP1.
| 1 5
USP46 inhibits YAP1. 6 / 6
| 1 5

reach
"Indeed, USP46 inhibition significantly increased YAP1, as well as the proliferation and metastasis of HCC cells."

reach
"Moreover, we discovered that USP46 inhibits YAP1 to reduce HCC cell growth and metastasis."

eidos
"Mechanistically , USP46 promotes the degradation of YAP1 by increasing expression of MST1 , and the increase in MST1 protein antagonizes YAP1 to suppress HCC progression ."

reach
"USP46 may promote degradation of YAP1 by stabilizing MST1 but not LATS1."

reach
"Our results revealed that the tumor suppressor function of USP46 in HCC was accomplished by inhibiting YAP1 expression.To explore the molecular mechanism by which USP46 regulates YAP1, we examined the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The results indicate that USP46 indirectly promotes the degradation of YAP1."
USP46 decreases the amount of YAP1.
| 5
USP46 decreases the amount of YAP1. 5 / 5
| 5

reach
"As expected, western blotting results revealed that overexpression of USP46 significantly decreased YAP1 protein expression, as well as expression of CTGF, the target gene of YAP."

reach
"In contrast, overexpression of USP46 dramatically suppressed the expression of YAP1 in HCC cells."

reach
"In this study, we found that USP46 also suppresses expression of YAP1, which further broadens the application of USP46 in cancer research.It is well known that the regulation mechanism of YAP1 is comp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"These results suggest that USP46 indirectly reduces YAP1 expression by disrupting MST1 expression.Several studies have suggested that expression of MST1 is decreased in many human cancers, including H[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"However, silencing USP46 markedly increased protein levels of both YAP1 and CTGF in HCC cells ( Fig. 4 A and B)."
USP46 binds YAP1.
| 2
| 2

sparser
"Importantly, the co-IP assay showed that USP46 does not directly interact with YAP1 but interacts with MST1 in HCC cells."

sparser
"However, our immunoprecipitation results demonstrated that there was no direct interaction between USP46 and YAP1 ( Supplementary Fig. S2 E )."
USP46 activates YAP1.
| 2
USP46 activates YAP1. 2 / 2
| 2

reach
"Our results revealed that upregulation of USP46 leads to decreased nuclear localization of YAP1, while downregulation of USP46 increased the nuclear localization of YAP1 ( Supplementary Fig. S2 B )."

reach
"In the present study, we clarified the mechanisms by which USP46 mediates the downregulation of YAP1 in HCC."
DTL affects USP46
| 15
| 10

sparser
"E6 protein promotes the interaction of USP46 with Cdt2."

sparser
"Thus there was a perfect correlation between an E6 variant’s ability to bind USP46 and promote the interaction of USP46 with Cdt2, and the ability of the variant to stabilize Cdt2."

sparser
"Concurrently, E6 forms a complex with the deubiquitinating enzyme USP46 in cervical cancer cells, promoting interaction between USP46 and Cdt2 (a component of the CRL4 Cdt2 E3 ubiquitin ligase complex)."

sparser
"Therefore although our co-immunoprecipitation experiments showed that DDB1 is present in the USP46:Cdt2 complex [ xref ], neither DDB1 nor a substrate of the CRL4-Cdt2 complex is required for the E6:USP46:Cdt2 interaction and subsequent Cdt2 stabilization"

sparser
"Immunoprecipitation of endogenous cellular Cdt2 coimmunoprecipitated cellular USP46 and E6 only from HeLa cell lysates (that contain HPV E6) but not from U2OS cell lysates (that do not contain E6) ( xref ; xref ), suggesting that E6 is necessary to promote the interaction of Cdt2 with USP46."

sparser
"In contrast, Flag-Cdt2 alone from cells without E6 did not co-immunoprecipitate endogenous USP46 ( xref , lane 1), suggesting that Cdt2 and USP46 do not interact with each other in the absence of E6."

sparser
"Thus, HPV E6 binds directly to USP46, and this facilitates the interaction of USP46 with its potential substrate Cdt2."

sparser
"Only high risk but not low risk E6 proteins could promote Cdt2 interaction with USP46 and stabilize Cdt2."

sparser
"If the interaction of USP46 with Cdt2 is essential for the stabilization of Cdt2, we would expect that the residues of E6 required to stabilize Cdt2 are also essential to promote the interaction of USP46 with Cdt2."

sparser
"Immunoprecipitation of Cdt2 and immunoblotting of the precipitate for USP46 showed that high risk 16E6 and the 1–43 fragment of 16E6, but not low risk 6E6 or 16E6-F2V/P5R, promoted the interaction of USP46 and Cdt2 ( xref ), demonstrating the correlation expected above."
E6 binds USP46 and DTL. 3 / 3
| 3

sparser
"The elution profile also suggests that the Cdt2 associates with E6-USP46, as a low-affinity substoichiometric substrate rather than as a core member of the E6-USP46 complex."

sparser
"In Hela cells, E6 is associates with E6AP and p53, and now we find that the E6 protein also associates with USP46 and Cdt2."

sparser
"We propose that the E6-USP46 interaction promotes the tripartite E6-USP46-Cdt2 complex either due to allosteric changes in USP46, or because Cdt2 interacts simultaneously with sites on E6 and USP46 ( xref )."
USP6 binds USP46 and DTL. 1 / 1
| 1

sparser
"Moreover, miR-3680-5p was associated with the USP6 , USP32 , USP46 , and DTL genes, which have roles in the ubiquitin (deubiquitin) proteolysis system."
USP46 binds DTL and IL17RB. 1 / 1
| 1

sparser
"Immunoprecipitates of myc-USP46 contained Cdt2 and DDB1 indicating that USP46 associates with CRL4-Cdt2 complex ( xref )."
LuxY affects USP46
| 14
| 14

sparser
"To generate YFP-USP12 delMEIL , YFP-USP46 +MEIL and YFP-WDR20 deletion mutants, the corresponding DNA sequences were amplified by PCR and cloned into pEYFP-C1 using BamHI/HindIII."

sparser
"A statistically significant, but very limited, increase in the N/C ratio of YFP-USP46 was noted."

sparser
"The most striking finding was the relocation of YFP-USP12, but not YFP-USP46 to the PM when co-expressed with Myc-WDR20."

sparser
"In line with previous studies ( Urbé et al., 2012 ; Lehoux et al., 2014 ), we found that YFP-USP12 and YFP-USP46 were located predominantly in the cytoplasm of 293 T and HeLa cells when expressed alon[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"YFP-USP46 plasmid was obtained by subcloning USP46 cDNA from a previously described plasmid ( Olazabal-Herrero et al., 2015 ) into pEYFP-C1 using BamHI/HindIII restriction sites."

sparser
"We used a similar knockdown/overexpression approach to asses a potential effect of WDR20 on the localization of YFP-USP12 and YFP-USP46."

sparser
"Image analysis showed that the nuclear to cytoplasmic ratio of YFP-USP46 was significantly higher when expressed with Myc-WDR20 NESm than with wild type Myc-WDR20 (Additional File 4b), suggesting that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Similar to UAF1 knockdown, WDR20 siRNA had no obvious effect on the localization of YFP-USP12 or YFP-USP46 ( Fig. 2 a)."

sparser
"Whereas YFP-USP46 and Myc-WDR20 co-localized diffusely throughout the cytoplasm, YFP-USP12 and Myc-WDR20 co-localized at the cell periphery ( Fig. 2 b)."

sparser
"In order to asses a potential effect of UAF1 on the localization of YFP-USP12 and YFP-USP46, cellular levels of UAF1 were either reduced using small interfering RNA (siRNA)-mediated knockdown or incre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
WDR48 affects USP12
| 13
| 8

sparser
"In addition to USP1, two other DUBs, USP12 and USP46 interact with UAF1 [ xref ], but the UAF1-binding sites in these DUBs have not yet been mapped."

sparser
"Recent crystallographic studies demonstrate that UAF1 binds to a distinct site on USP12 or USP46 and, through an allosteric interaction, stimulates DUB activity ( xref ; xref )."

sparser
"In C. elegans , USP46 and USP12 both bind to USP1-associated factor 1 (UAF1/WDR48) and the binding dramatically enhances the activity of USP12 and USP46 ( xref , xref ; xref )."

sparser
"The mode of interaction of USP12 and USP46 with UAF1 is still unclear."

sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."

sparser
"UAF1 also interacts with DUBs USP12 and USP46 ( García-Santisteban et al., 2013 ) and, thus, both genes also could be involved in senescence."

sparser
"P65 interacted with USP12, USP46 and UAF1 in both resting and LPS-stimulated macrophages, but exhibited no association with USP1 (Fig.  xref )."

sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
USP46 affects Ubiquitin
| 3 10
USP46 binds Ubiquitin.
| 2 10

sparser
"We superimposed the crystal structures of USP46 in a non-covalent complex with WDR20 and WDR48 together with the covalent USP46ubiquitin complex."

sparser
"The USP46-bound ubiquitin is closer, however, sheltered adjacent to the concave inner face of the WDR48 ancillary domain."

sparser
"Binding of WDR20 to the UAF1-USP12 complex induces multiple structural changes in the enzyme, converting it into a compact form similar to Ub-bound USP46."

reach
"Binding of WDR20 to the UAF1 and USP12 complex induces multiple structural changes in the enzyme, converting it into a compact form similar to Ub bound USP46."

sparser
"Furthermore, difference density indicating the missing domain clearly extended from our extant WDR48 C terminus, encircling the USP46-bound ubiquitin and approaching the thumb subdomain of USP46 over [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Reminiscent of the Ub bound UAF1 and USP46 complex, the UAF1-USP12 structure features an L shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme (XREF_FIG and XREF_FIG)."

sparser
"Stabilization of a malleable apo USP46 to favor an active conformation would shift the equilibrium of association and promote productive interaction between ubiquitin and USP46."

sparser
"UAF1 activation of USP12 requires structural fine-tuning at the ubiquitin-binding site, while WDR20 directly regulates the catalytic center of the enzyme remotely, transforming USP12 into a compact structure similar to USP46-Ub [ xref ]."

sparser
"Jianping Yin et al determined the 1.9A ° resolution structure of a resolution structure of a covalently attached USP46 25–366 ubiquitin complex."

sparser
"The substrate is cradled between the fingers and the inner palm/thumb regions. xref Moreover, a Zintegrated by 4 conserved Cys residues stabilizes the USP46 subdomain of the tip of the fingers, and the active-site adopts a catalytically favorable conformation. xref The USP46:ubiquitin interface buries 1,825A ° 2 of surface area on each protein."
| 1

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme ( xref and xref )."
USP46 inhibits Ubiquitin.
| 1
| 1

reach
"In TAMR-MCF-7 cells, USP46 is significantly overexpressed, preventing the ubiquitin-mediated degradation of PTBP152."
USP12 affects WDR48
| 13
| 8

sparser
"In addition to USP1, two other DUBs, USP12 and USP46 interact with UAF1 [ xref ], but the UAF1-binding sites in these DUBs have not yet been mapped."

sparser
"Recent crystallographic studies demonstrate that UAF1 binds to a distinct site on USP12 or USP46 and, through an allosteric interaction, stimulates DUB activity ( xref ; xref )."

sparser
"In C. elegans , USP46 and USP12 both bind to USP1-associated factor 1 (UAF1/WDR48) and the binding dramatically enhances the activity of USP12 and USP46 ( xref , xref ; xref )."

sparser
"The mode of interaction of USP12 and USP46 with UAF1 is still unclear."

sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."

sparser
"UAF1 also interacts with DUBs USP12 and USP46 ( García-Santisteban et al., 2013 ) and, thus, both genes also could be involved in senescence."

sparser
"P65 interacted with USP12, USP46 and UAF1 in both resting and LPS-stimulated macrophages, but exhibited no association with USP1 (Fig.  xref )."

sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
WDR48 affects WDR20
| 9 3
| 9 2

reach
"These recent structural and biochemical studies complement in vivo studies of the USP-46, WDR-48, and WDR-20 complex in C. elegans."

reach
"Total levels of WDR48 and USP46 were unchanged upon 4HT withdrawal (XREF_FIG) thus increased signal in the WDR48 ChIP at the p14 was not attributable to increased expression of the constituents of the USP46, WDR48, and WDR20 complex by EBNA3C."

reach
"The overall structure of the USP46-WDR48-WDR20 complex is very similar to that of the USP12-WDR48-WDR20 complex."

reach
"Thus, the steady-state localization of the USP46/UAF1/WDR20 complex was cytoplasmic, while the USP12/UAF1/WDR20 complex localized mainly to the plasma membrane (PM)."

reach
"Because USP46 and USP12 are highly homologous (~ 90% identity) and we could confirm a robust association with USP46 by Western blotting (discussed below), we chose to focus our subsequent attention on the USP46, WDR48, and WDR20 complex."

reach
"Because our TAP lysis procedure extracted both nuclear and cytoplasmic proteins (XREF_SUPPLEMENTARY), we wanted to ensure that the USP46, WDR48, and WDR20 complex subcellular localization was compatible with formation of a complex with EBNA3 proteins."

reach
"Together with data showing that co-expression of the USP-46, WDR-48, and WDR-20 complex reduces levels of ubiquitinated GLR-1, these results support a model wherein USP-46, when bound to WDR-48 and WDR-20, deubiquitinates GLR-1 and increases receptor stability and function in vivo."

reach
"To determine whether the USP46-UAF1-WDR20 complex regulates Wnt signaling in physiological contexts, we took a loss-of-function approach in Drosophila."

sparser
"USP46 is normally associated with its accessory proteins UAF1 and WDR20."

sparser
"These results indicate that USP46 does not associate with its accessory factor UAF1 or WDR20 when interacting with or deubiquitinating Cdt2 in high risk E6 transformed cells."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
Ubiquitin affects USP46
| 2 10

sparser
"We superimposed the crystal structures of USP46 in a non-covalent complex with WDR20 and WDR48 together with the covalent USP46ubiquitin complex."

sparser
"The USP46-bound ubiquitin is closer, however, sheltered adjacent to the concave inner face of the WDR48 ancillary domain."

sparser
"Binding of WDR20 to the UAF1-USP12 complex induces multiple structural changes in the enzyme, converting it into a compact form similar to Ub-bound USP46."

reach
"Binding of WDR20 to the UAF1 and USP12 complex induces multiple structural changes in the enzyme, converting it into a compact form similar to Ub bound USP46."

sparser
"Furthermore, difference density indicating the missing domain clearly extended from our extant WDR48 C terminus, encircling the USP46-bound ubiquitin and approaching the thumb subdomain of USP46 over [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Reminiscent of the Ub bound UAF1 and USP46 complex, the UAF1-USP12 structure features an L shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme (XREF_FIG and XREF_FIG)."

sparser
"Stabilization of a malleable apo USP46 to favor an active conformation would shift the equilibrium of association and promote productive interaction between ubiquitin and USP46."

sparser
"UAF1 activation of USP12 requires structural fine-tuning at the ubiquitin-binding site, while WDR20 directly regulates the catalytic center of the enzyme remotely, transforming USP12 into a compact structure similar to USP46-Ub [ xref ]."

sparser
"Jianping Yin et al determined the 1.9A ° resolution structure of a resolution structure of a covalently attached USP46 25–366 ubiquitin complex."

sparser
"The substrate is cradled between the fingers and the inner palm/thumb regions. xref Moreover, a Zintegrated by 4 conserved Cys residues stabilizes the USP46 subdomain of the tip of the fingers, and the active-site adopts a catalytically favorable conformation. xref The USP46:ubiquitin interface buries 1,825A ° 2 of surface area on each protein."
| 1

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme ( xref and xref )."
USP46 affects WDR20, and WDR48
| 9 2
| 9 2

reach
"These recent structural and biochemical studies complement in vivo studies of the USP-46, WDR-48, and WDR-20 complex in C. elegans."

reach
"Total levels of WDR48 and USP46 were unchanged upon 4HT withdrawal (XREF_FIG) thus increased signal in the WDR48 ChIP at the p14 was not attributable to increased expression of the constituents of the USP46, WDR48, and WDR20 complex by EBNA3C."

reach
"The overall structure of the USP46-WDR48-WDR20 complex is very similar to that of the USP12-WDR48-WDR20 complex."

reach
"Thus, the steady-state localization of the USP46/UAF1/WDR20 complex was cytoplasmic, while the USP12/UAF1/WDR20 complex localized mainly to the plasma membrane (PM)."

reach
"Because USP46 and USP12 are highly homologous (~ 90% identity) and we could confirm a robust association with USP46 by Western blotting (discussed below), we chose to focus our subsequent attention on the USP46, WDR48, and WDR20 complex."

reach
"Because our TAP lysis procedure extracted both nuclear and cytoplasmic proteins (XREF_SUPPLEMENTARY), we wanted to ensure that the USP46, WDR48, and WDR20 complex subcellular localization was compatible with formation of a complex with EBNA3 proteins."

reach
"Together with data showing that co-expression of the USP-46, WDR-48, and WDR-20 complex reduces levels of ubiquitinated GLR-1, these results support a model wherein USP-46, when bound to WDR-48 and WDR-20, deubiquitinates GLR-1 and increases receptor stability and function in vivo."

reach
"To determine whether the USP46-UAF1-WDR20 complex regulates Wnt signaling in physiological contexts, we took a loss-of-function approach in Drosophila."

sparser
"USP46 is normally associated with its accessory proteins UAF1 and WDR20."

sparser
"These results indicate that USP46 does not associate with its accessory factor UAF1 or WDR20 when interacting with or deubiquitinating Cdt2 in high risk E6 transformed cells."
STK4 affects USP46
2 | 4 5
STK4 binds USP46.
2 | 2 5
2 | 2 5

sparser
"In conclusion, we found that USP46 interacts with MST1 and decreases the polyubiquitination of MST1, stabilizing MST1 and leading to the inactivation of YAP1 in HCC."

sparser
"To test this hypothesis, we first validated the specificities of USP46 and MST1 interactions in HCC cells."

No evidence text available

sparser
"As expected, co-IP assays confirmed the interaction between USP46 and MST1 using endogenous USP46 and MST1 antibodies in Huh-7 and Hep3B cells ( Fig. 6 A)."

No evidence text available

sparser
"In addition, we revealed that USP46 interacts with the Hippo pathway core component MST1."

reach
"To test this hypothesis, we first validated the specificities of USP46 and MST1 interactions in HCC cells."

reach
"As expected, co-IP assays confirmed the interaction between USP46 and MST1 using endogenous USP46 and MST1 antibodies in Huh-7 and Hep3B cells ( Fig. 6 A)."

sparser
"Furthermore, USP46 directly binds to the MST1 protein and lowers its ubiquitination, stabilizing it."
STK4 increases the amount of USP46.
| 1
STK4 increases the amount of USP46. 1 / 1
| 1

reach
"Conversely, downregulation of MST1 rescued YAP1 protein expression in USP46-overexpressing Huh-7 cells and improved cell proliferation and invasion ability ( Fig. 5 F–H)."
STK4 decreases the amount of USP46.
| 1
STK4 decreases the amount of USP46. 1 / 1
| 1

reach
"Inhibition of MST1 rescued YAP1 protein expression in USP46-overexpressing HCC cells."
USP46 affects Neoplasms
| 10
USP46 activates Neoplasms.
| 7
| 7

reach
"However, in esophageal squamous cell carcinoma and cervical cancer (CC), USP46 increases tumor growth."

reach
"These results reveal the tumor-promoting activity of USP46 in melanoma is mainly through deubiquitinating and stabilizing NRAS Q61R/K mutants."

reach
"Our studies illustrated that USP46 could strikingly promote cell migration, invasion and tumor metastasis of ESCC."

reach
"Moreover, tumorigenicity assays showed that compared to cells overexpressing USP46, restoring YAP1 expression in cells overexpressing USP46 promoted tumor growth ( Fig. 4 F and G)."

reach
"In contrast, a different study showed that USP46 promotes proliferation and tumor growth of HPV-transformed cancers [ 27 ]."

reach
"These results implicated that USP46 promotes ESCC tumor metastasis in a catalytic-dependent way."

reach
"In addition to affecting the proliferation of cancer cells, USP46 has also been demonstrated to promote tumor metastasis by stabilizing ENO1 in human esophageal squamous cell carcinoma [ 28 ]."
USP46 inhibits Neoplasms.
| 3
| 3

reach
"This result indicates that upregulation of USP46 inhibits tumor proliferation and growth.In contrast, we used two USP46-specific short hairpin RNA (shUSP46-1, shUSP46-2) plasmids to reduce USP46 expre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Our data indicate that USP46 represses RCC tumor progression via the inhibition of the AKT signaling pathway."

reach
"In addition, USP46 functions as an MST1 DUB, enhancing MST1 kinase activity to inhibit tumor development and metastasis."
USP46 affects ENO1
1 | 6 3
USP46 binds ENO1.
| 2 3
| 2 3

reach
"The interaction between USP46 and ENO1 was proved by the co-immunoprecipitation assay reciprocally ( Fig. 5 B and C)."

reach
"In addition, USP46 interacts with ENO1 and stabilizes ENO1 through deubiquitination, and high USP46 and ENO1 expression indicates positive lymph node metastasis and advanced clinical stages in ESCC sa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In addition, USP46 interacts with ENO1 and stabilizes ENO1 through deubiquitination, and high USP46 and ENO1 expression indicates positive lymph node metastasis and advanced clinical stages in ESCC sa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The interaction between USP46 and ENO1 was proved by the co-immunoprecipitation assay reciprocally ( Fig. 5 B and C)."

sparser
"As we expected, USP46 interacts with ENO1 and the two proteins are co-localized primarily in ESCC cells."
USP46 activates ENO1.
| 3
USP46 activates ENO1. 3 / 3
| 3

reach
"These results indicated that USP46 promotes ESCC cell metastasis through regulating ENO1.To further validate the relationship of USP46 and ENO1 in ESCC, we examined the expression of ENO1 in 48 clinic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In addition to affecting the proliferation of cancer cells, USP46 has also been demonstrated to promote tumor metastasis by stabilizing ENO1 in human esophageal squamous cell carcinoma [ 28 ]."

reach
"Increased USP46 prolonged the half-life of ENO1 by antagonizing ENO1 ubiquitination and inhibiting ENO1 proteasome-associated degradation."
USP46 increases the amount of ENO1.
| 1
USP46 increases the amount of ENO1. 1 / 1
| 1

reach
"We identified that USP46 upregulation increases ENO1 expression in ESCC and subsequently leads to the accelerated ESCC metastasis."
USP46 deubiquitinates ENO1.
1 |
USP46 deubiquitinates ENO1. 1 / 1
1 |

"In addition, we found that <span class="match term0">USP46</span> is a bona fide deubiquitinating enzyme to stabilize the protein level of <span class="match term1">ENO1</span> through deubiquitination"
CSNK1 affects USP46
| 10
CSNK1 phosphorylates USP46.
| 9
CSNK1 phosphorylates USP46. 9 / 9
| 9

reach
"We next investigated whether CK1δ could phosphorylate USP46."

reach
"Mechanistically, CK1δ-mediated phosphorylation of USP46 is a critical post-translational mechanism that controls stability and oncogenic function of these NRAS mutants."

reach
"Mechanistically, CK1δ directly phosphorylates and activates USP46, thereby promoting oncogenic NRAS-driven melanocyte transformation and tumor progression."

reach
"CK1δ-mediated phosphorylation of USP46 in the in vitro kinase assay was detected by using phospho-tag gel, which was significantly mitigated by the treatment of PF670462 (Fig. 6d)."

reach
"As shown in Supplementary Fig. 9c, CK1δ significantly increased the phosphorylation of USP46 WT assessed by anti-p-Ser and anti-p-Thr antibodies, whereas the 3A mutant could largely decrease such phosphorylation events."

reach
"These results suggest that CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity toward NRAS Q61R."

reach
"Next, we examined the effect of CK1δ-mediated phosphorylation of USP46 on the ubiquitination of NRAS mutants."

reach
"These results indicate that CK1δ stabilizes NRAS mutant in melanoma in a USP46-dependent manner.We next investigated the function of CK1δ-mediated phosphorylation of USP46 on oncogenic NRAS-dependent malignant processes."

reach
"These results indicate that CK1δ-mediated phosphorylation of USP46 is pivotal to stabilize NRAS mutant and promote oncogenic NRAS-dependent tumor progression."
CSNK1 binds USP46.
| 1
| 1

reach
"Second, CK1δ binds and regulates the phosphorylation of USP46 (Fig. 6 and Supplementary Fig. 9)."
USP46 affects USP1
1 | 1 7
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
1 | 1

No evidence text available

reach
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."
WDR48 binds USP1 and USP46. 2 / 2
| 2

sparser
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."

sparser
"Also, UAF1 can interact with USP1 and USP46 in addition to USP12 [ xref ]."
USP1 binds USP12 and USP46. 2 / 2
| 2

sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."

sparser
"UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46."
| 1 5

eidos
"In functional experiments , overexpression of USP46 impaired proliferation and metastasis of HCC cells , whereas knockdown of USP46 enhanced cell proliferation and invasiveness in vitro and in vivo ."

reach
"As shown in Fig. 3 A and B, upregulation of USP46 inhibited Huh-7 cell migration and invasion abilities in vitro ."

reach
"These experimental results indicate that USP46 inhibits the invasion and metastasis of hepatoma cells in vivo and in vitro ."

reach
"In functional investigations, USP46 knockdown increased cell proliferation and invasiveness in vitro and in vivo whereas overexpression of USP46 decreased HCC cell proliferation and metastasis."

reach
"We found that USP46 suppresses HCC cell proliferation, migration and invasion in vitro and metastasis in vivo , implying that USP46 may serve as a tumor suppressor in HCC."

reach
"However, tumor cells were resuspended in serum-free medium when we conducted invasion and migration assays, which showed that USP46 inhibits both the proliferation and invasion of HCC cells."
| 3

reach
"These findings demonstrated ENO1 as a novel downstream substrate of USP46 and is stabilized by USP46 via deubiquitination.Furthermore, to further identify that USP46 promoted ESCC migration and invasi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"As shown in Fig. 4 , overexpression of YAP1 enhanced HCC cell proliferation and invasion abilities, and re-expression of YAP1 attenuated the decrease in proliferation and invasion induced by overexpre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Our studies illustrated that USP46 could strikingly promote cell migration, invasion and tumor metastasis of ESCC."
USP1 affects USP46
1 | 1 7
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
1 | 1

No evidence text available

reach
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."
WDR48 binds USP1 and USP46. 2 / 2
| 2

sparser
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."

sparser
"Also, UAF1 can interact with USP1 and USP46 in addition to USP12 [ xref ]."
USP1 binds USP12 and USP46. 2 / 2
| 2

sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."

sparser
"UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46."
ENO1 affects USP46
| 6 3
ENO1 binds USP46.
| 2 3
| 2 3

reach
"The interaction between USP46 and ENO1 was proved by the co-immunoprecipitation assay reciprocally ( Fig. 5 B and C)."

reach
"In addition, USP46 interacts with ENO1 and stabilizes ENO1 through deubiquitination, and high USP46 and ENO1 expression indicates positive lymph node metastasis and advanced clinical stages in ESCC sa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In addition, USP46 interacts with ENO1 and stabilizes ENO1 through deubiquitination, and high USP46 and ENO1 expression indicates positive lymph node metastasis and advanced clinical stages in ESCC sa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The interaction between USP46 and ENO1 was proved by the co-immunoprecipitation assay reciprocally ( Fig. 5 B and C)."

sparser
"As we expected, USP46 interacts with ENO1 and the two proteins are co-localized primarily in ESCC cells."
ENO1 increases the amount of USP46.
| 2
ENO1 increases the amount of USP46. 2 / 2
| 2

reach
"Subsequently, we transfected HEK293T cells with increasing concentration of USP46 plasmids and the same concentration of ENO1 plasmids for 24 h. With the rising amount of USP46 expression, the protein[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Transwell assay showed that decreased ENO1 expression partially reversed the effect of USP46 overexpression( Fig. S2B )."
ENO1 activates USP46.
| 2
ENO1 activates USP46. 2 / 2
| 2

reach
"These findings demonstrated ENO1 as a novel downstream substrate of USP46 and is stabilized by USP46 via deubiquitination.Furthermore, to further identify that USP46 promoted ESCC migration and invasi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Increased USP46 prolonged the half-life of ENO1 by antagonizing ENO1 ubiquitination and inhibiting ENO1 proteasome-associated degradation."
DMWD affects USP46
7 | 1 1
DMWD binds USP46.
7 | 1
7 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
DMWD binds USP12 and USP46. 1 / 1
| 1

sparser
"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
DMWD activates USP46.
| 1
DMWD activates USP46. 1 / 1
| 1

reach
"USP12 and USP46, consisting of only a USP domain [4], share 88% amino acid sequence homology and are potentiated by WDR48, WDR20, and DMWD [8, 9, 10]."
USP46 affects USP46
| 8
USP46 dephosphorylates USP46.
| 2
USP46-S354A leads to the dephosphorylation of USP46. 1 / 1
| 1

reach
"The single mutation of USP46 T209A, S351A or S354A only mildly decreased the phosphorylation of USP46, while the 3A mutant (T209A/S351A/S354A) almost completely abolished it assessed by phospho-tag gel (Fig. 6e)."
USP46-T209A leads to the dephosphorylation of USP46. 1 / 1
| 1

reach
"The single mutation of USP46 T209A, S351A or S354A only mildly decreased the phosphorylation of USP46, while the 3A mutant (T209A/S351A/S354A) almost completely abolished it assessed by phospho-tag gel (Fig. 6e)."
USP46 ubiquitinates USP46.
| 1
USP46 leads to the ubiquitination of USP46. 1 / 1
| 1

reach
"Stabilization of a malleable apo USP46 to favor an active conformation would shift the equilibrium of association and promote productive interaction between ubiquitin and USP46."
USP46 phosphorylates USP46.
| 1
USP46-S351A leads to the phosphorylation of USP46. 1 / 1
| 1

reach
"The single mutation of USP46 T209A, S351A or S354A only mildly decreased the phosphorylation of USP46, while the 3A mutant (T209A/S351A/S354A) almost completely abolished it assessed by phospho-tag gel (Fig. 6e)."
USP46 inhibits USP46.
| 1
USP46 inhibits USP46. 1 / 1
| 1

reach
"In addition, the expression of USP46 was significantly decreased in 60% of colorectal cancer samples (P < 0.01) indicating a potential tumor suppressor role of USP46."
USP46 deubiquitinates USP46.
| 1
USP46 deubiquitinates USP46. 1 / 1
| 1

reach
"Given the same type of deubiquitinating enzyme (USP46) is able to deubiquitinate AMPA receptors, and knockdown of USP46 elevated AMPA receptor ubiquitination and reduced AMPA receptor expression in hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 decreases the amount of USP46.
| 1
USP46 decreases the amount of USP46. 1 / 1
| 1

reach
"Concomitant expression of Cas9 and Usp46 sgRNAs in the posterior compartment using hh-Gal4 reduced Usp46 levels in the posterior compartment, as revealed by loss of the Usp46-V5 signal (Fig. S5D, F)."
USP46 activates USP46.
| 1
USP46 bound to WDR48 activates USP46. 1 / 1
| 1

reach
"In C. elegans, USP46 and USP12 both bind to USP1 associated factor 1 (UAF1 and WDR48) and the binding dramatically enhances the activity of USP12 and USP46."
USP46 affects Histone_H2B
| 8
USP46 deubiquitinates Histone_H2B. 8 / 8
| 8

reach
"Usp12 and Usp46 deubiquitinate both H2A and H2B and Uaf-1 is required for this reaction [XREF_BIBR]."

reach
"USP12 and USP46 prefer nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and in vivo."

reach
"In other species, USP46 deubiquitinates deubiquitinate histones H2A and H2B associated to USP12 and WDR48 proteins, reinforcing its epigenetic function [40]."

reach
"USP12 and USP46 can deubiquitinate histones H2A and H2B, thereby playing a critical role in Xenopus development [91] ."

reach
"A recently found DUBs called ubiquitin-specific protease 46 (USP46) was shown to catalyze the deubiquitination of H2A and H2B for the initial time and may aid in the cultivation of Xenopus."

reach
"Joo et al. demonstrated that USP46 and USP12 containing fractions from HeLa cells can deubiquitinate histones H2A and H2B to control cell fate and gastrulation during Xenopus development [XREF_BIBR]."

reach
"Both USP12 and USP46 deubiquitinate histone H2A and H2B, affecting Xenopus development (Joo et al., 2011), and, unlike USP1, these smaller USPs can simultaneously bind WDR20 in addition to WDR48 (Joo [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"It has also been reported that USP12 and USP46 deubiquitinate histone H2A and H2B thereby playing a role in Xenopus development."
USP46 affects DMWD
7 | 1
7 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
DMWD binds USP12 and USP46. 1 / 1
| 1

sparser
"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
USP12 affects USP46, and WDR48
| 8
| 8

sparser
"In addition to USP1, two other DUBs, USP12 and USP46 interact with UAF1 [ xref ], but the UAF1-binding sites in these DUBs have not yet been mapped."

sparser
"Recent crystallographic studies demonstrate that UAF1 binds to a distinct site on USP12 or USP46 and, through an allosteric interaction, stimulates DUB activity ( xref ; xref )."

sparser
"In C. elegans , USP46 and USP12 both bind to USP1-associated factor 1 (UAF1/WDR48) and the binding dramatically enhances the activity of USP12 and USP46 ( xref , xref ; xref )."

sparser
"The mode of interaction of USP12 and USP46 with UAF1 is still unclear."

sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."

sparser
"UAF1 also interacts with DUBs USP12 and USP46 ( García-Santisteban et al., 2013 ) and, thus, both genes also could be involved in senescence."

sparser
"P65 interacted with USP12, USP46 and UAF1 in both resting and LPS-stimulated macrophages, but exhibited no association with USP1 (Fig.  xref )."

sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
| 7
| 4

reach
"The up-regulated expression level of deubiquitinating enzyme USP46 induces the apoptosis of A549 cells by TRAF6."

reach
"These findings collectively suggest that the up-regulated USP46 promotes apoptosis in lung cancer cells through the regulation of TRAF6."

reach
"In SKOV3 and DDP cells, the upregulation of USP46 expression levels notably suppressed cell viability and increased cell apoptosis."

reach
"Furthermore, the overexpression of PUM2 in SKOV3 and DDP cells partially recovered the suppressive effect over proliferation and the increased levels of apoptosis induced by the overexpression of USP46."
| 3

reach
"As shown in Supplementary Fig. 6e, the depletion of USP46 in genetically engineered human immortalized melanocytes (hTERT/CDK4 /p53 ) expressing NRAS Q61R induced a significant reduction of cell proliferation as assessed by Ki67 staining, and a significant increase of apoptotic cell death as assessed by cleaved caspase-3 staining."

reach
"The USP46 downregulation is associated with increased cell viability and inhibited apoptosis [59] ."

reach
"The downregulation of USP46 expression levels in SKOV3 cells significantly inhibited cell apoptosis and increased cell viability."
NRAS affects USP46
| 1 6
| 6

sparser
"Similarly, the interaction of USP46 and NRAS Q61R is much stronger than NRAS WT pretreated with GDP or GTPγS (Fig. xref )."

sparser
"The direct interaction of USP46 and NRAS mutants prompt us to examine whether USP46 is essential to regulate the stability and oncogenic function of NRAS mutants."

sparser
"In our study, the interaction of USP46 with NRAS WT and Q61L mutant is weaker than NRAS Q61R or Q61K (Fig. xref ), which might be due to the conformation difference and charge alterations between the positively charged mutations (Q61R and Q61K) and non-polar mutation (Q61L)."

sparser
"The endogenous interaction between USP46 and NRAS Q61R was validated in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells, respectively (Fig. xref and Supplementary Fig.  xref )."

sparser
"We also examined the interaction between purified USP46 and different NRAS mutants."

sparser
"The basic amino acids K61 and R61 could form a salt bridge with the acidic residue E333 of USP46, thereby enhancing the interaction between USP46 and NRAS Q61K/R mutants."
USP46 binds NRAS-Q61R. 1 / 1
| 1

reach
"The endogenous interaction between USP46 and NRAS Q61R was validated in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells, respectively (Fig. 3c, d and Supplementary Fig. 3a)."
GLR1.1 affects USP46
| 5 2
GLR1.1 binds USP46.
| 3 2
| 2 2

reach
"First, we tested whether USP-46 could interact with GLR-1, as might be expected if GLR-1 were a deubiquitination target of USP-46."

sparser
"Biochemical results indicate that although bacterially-expressed recombinant USP46 can interact with GLR-1 from worm extracts, it only exhibits a low level of DUB activity [ xref ]."

sparser
"In the ventral nerve cord of C. elegans it was found that USP46 binds to GLR-1, and negatively regulates the levels of its ubiquitination."

reach
"In the ventral nerve cord of C. elegans it was found that USP46 binds to GLR-1, and negatively regulates the levels of its ubiquitination."
USP46 binds ubiquitinated GLR1.1. 1 / 1
| 1

reach
"Since recombinant GST-GLR-1C is not ubiquitinated, these data are consistent with the idea that USP-46 binds to ubiquitinated GLR-1, which has previously been shown to make up less than 0.5% of total GLR-1 in worms."
GLR1.1 activates USP46.
| 2
GLR1.1 activates USP46. 2 / 2
| 2

reach
"First, we tested whether USP-46 could interact with GLR-1, as might be expected if GLR-1 were a deubiquitination target of USP-46."

reach
"To further test whether USP-46 regulation of reversal frequencies is mediated by GLR-1, we examined if usp-46 mutation could suppress the effects of a dominant-active version of GLR-1 (GLR-1 (A/T)), on locomotion behavior."
CK1δ affects USP46
| 7
CK1δ phosphorylates USP46.
| 4
CK1δ phosphorylates USP46. 4 / 4
| 4

sparser
"CK1δ binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."

sparser
"We next investigated whether CK1δ could phosphorylate USP46."

sparser
"These results suggest that CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity toward NRAS Q61R."

sparser
"As shown in Supplementary Fig.  xref , CK1δ significantly increased the phosphorylation of USP46 WT assessed by anti-p-Ser and anti-p-Thr antibodies, whereas the 3A mutant could largely decrease such phosphorylation events."
CK1δ binds USP46.
| 3
CK1δ binds USP46. 3 / 3
| 3

sparser
"CK1δ binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."

sparser
"In addition, purified GST-CK1δ protein could pull-down His-USP46 in a cell-free system, indicating the direct interaction between CK1δ and USP46 (Fig. xref )."

sparser
"The endogenous USP46-CK1δ interaction were validated in SK-MEL-103 and SK-MEL-30 cells, respectively (Fig. xref and Supplementary Fig.  xref )."
USP46 affects Wingless
| 6
USP46 activates Wingless.
| 3
USP46 activates Wingless. 3 / 3
| 3

reach
"The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6."

reach
"Together, these findings provide additional evidence that Usp46 promotes Wingless signaling in the larval wing disc.Inactivation of Wdr20 and Uaf1 using the same approach also decreased Wingless signaling in the wing disc."

reach
"These findings reveal that in a manner similar to known Wingless pathway components, the Usp46 complex non-autonomously restricts proliferation of neighboring ISCs, providing additional evidence that Usp46 promotes Wingless signaling during intestinal homeostasis."
USP46 inhibits Wingless.
| 2
USP46 inhibits Wingless. 2 / 2
| 2

reach
"Together, these findings provide additional evidence that Usp46 promotes Wingless signaling in the larval wing disc.Inactivation of Wdr20 and Uaf1 using the same approach also decreased Wingless signaling in the wing disc."

reach
"These findings reveal that in a manner similar to known Wingless pathway components, the Usp46 complex non-autonomously restricts proliferation of neighboring ISCs, providing additional evidence that Usp46 promotes Wingless signaling during intestinal homeostasis."
USP46 increases the amount of Wingless.
| 1
USP46 increases the amount of Wingless. 1 / 1
| 1

reach
"Furthermore, depletion of Usp46, Wdr20 or Uaf1 did not inhibit wingless expression, indicating that the observed reduction in Sens was not due to decreased Wingless levels, but instead resulted from impaired reception of the Wingless ligand or downstream defects in the Wingless signaling pathway (Fig. S3)."
USP46 affects PHLPP2
6 |
6 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP46 affects HYCC1
| 6
USP46 inhibits HYCC1.
| 5
USP46 inhibits HYCC1. 5 / 5
| 5

reach
"In summary, our results confirm that USP46 suppresses HCC proliferation and growth in vivo and in vitro ."

reach
"In functional investigations, USP46 knockdown increased cell proliferation and invasiveness in vitro and in vivo whereas overexpression of USP46 decreased HCC cell proliferation and metastasis."

reach
"Indeed, USP46 inhibition significantly increased YAP1, as well as the proliferation and metastasis of HCC cells."

reach
"However, tumor cells were resuspended in serum-free medium when we conducted invasion and migration assays, which showed that USP46 inhibits both the proliferation and invasion of HCC cells."

reach
"Furthermore, our results demonstrated that USP46 suppresses HCC proliferation and metastasis by inhibiting the MST1/YAP1 axis."
USP46 activates HYCC1.
| 1
USP46 activates HYCC1. 1 / 1
| 1

reach
"In the present study, we clarified the mechanisms by which USP46 mediates the downregulation of YAP1 in HCC."
PUM2 affects USP46
| 4 2
PUM2 binds USP46.
| 3 2
| 3 2

sparser
"The results of the RNA immunoprecipitation chip assay demonstrated that PUM2 bound to USP46 and regulated its expression."

sparser
"As shown in xref , the results of the RIP experiments revealed that PUM2 could bind to USP46 in SKOV3 and SKOV3/DDP cells."

reach
"The association between USP46 and PUM2 was assessed by RNA immunoprecipitation."

reach
"The results of the RNA immunoprecipitation chip assay demonstrated that PUM2 bound to USP46 and regulated its expression."

reach
"As shown in XREF_FIG, the results of the RIP experiments revealed that PUM2 could bind to USP46 in SKOV3 and SKOV3 and DDP cells."
PUM2 inhibits USP46.
| 1
PUM2 inhibits USP46. 1 / 1
| 1

reach
"Further experiments revealed that PUM2 attenuated the effects of USP46 on the expression levels of apoptosis related proteins and p-AKT and mTOR expression."
PHLPP2 affects USP46
6 |
6 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
LRP6 affects USP46
| 1 5
| 1 5

sparser
"Because the association of the USP46 complex with LRP6 was enhanced in the presence of Wnt stimulation (Fig.  xref ), we tested whether the USP46 complex interacted with LRP6 receptor aggregates in signalosomes that could be readily detected in sucrose density gradients xref ."

reach
"It remains to be determined whether the USP46 complex binds LRP6 as a pre-formed trimer or whether it proceeds through stepwise recruitment of individual subunits."

sparser
"It remains to be determined whether the USP46 complex binds LRP6 as a pre-formed trimer or whether it proceeds through stepwise recruitment of individual subunits."

sparser
"Wnt signaling promotes the binding of the USP46 complex to the Wnt coreceptor LRP6 at the cell surface, stabilizing LRP6 on the cell surface."

sparser
"The binding of the USP46 complex to LRP6 is enhanced by Wnt stimulation."

sparser
"Given its effect on LRP6 levels, we explored whether the USP46 complex interacted with LRP6."
WDR48 affects USP1
| 5
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
WDR48 binds USP1 and USP46. 2 / 2
| 2

sparser
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."

sparser
"Also, UAF1 can interact with USP1 and USP46 in addition to USP12 [ xref ]."
USP46 affects PUM2
| 3 2
| 3 2

sparser
"The results of the RNA immunoprecipitation chip assay demonstrated that PUM2 bound to USP46 and regulated its expression."

sparser
"As shown in xref , the results of the RIP experiments revealed that PUM2 could bind to USP46 in SKOV3 and SKOV3/DDP cells."

reach
"The association between USP46 and PUM2 was assessed by RNA immunoprecipitation."

reach
"The results of the RNA immunoprecipitation chip assay demonstrated that PUM2 bound to USP46 and regulated its expression."

reach
"As shown in XREF_FIG, the results of the RIP experiments revealed that PUM2 could bind to USP46 in SKOV3 and SKOV3 and DDP cells."
USP46 affects ILC3
| 5
USP46 binds ILC3. 5 / 5
| 5

sparser
"Additionally, ILC3USP46 enriched immune‐regulation‐related GO terms, such as ‘immune response‐activating cell surface receptor signalling’, ‘positive regulation of interferon‐gamma production’, ‘lymphocyte differentiation’, indicating its proinflammatory function."

sparser
"In the other branch, ILC3‐CCR7 cells progress through intermediate states, including ILC3USP46 and ILC3‐GNLY, towards transcriptional profiles resembling ILC1/NK cells (Figure  xref )."

sparser
"Intriguingly, unlike ILC3‐CCR7, which is enriched in the normal intestine, the other three subsets of ILC3s (ILC3USP46, ILC3‐GNLY and ILC3‐HSPA1B) are primarily distributed in CRC."

sparser
"Unsupervised clustering further identified four transcriptionally distinct subgroups, namely ILC3‐CCR7, ILC3‐HSPA1B, ILC3USP46 and ILC3‐GNLY (Figures  xref and xref )."

sparser
"ILC3USP46 displayed elevated expression of genes involved in cell adhesion and migration (e.g., SELL and CD38 ), and transcriptional regulation of immune responses (e.g., IRF8 )."
USP12 affects USP1
| 5
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
USP1 binds USP12 and USP46. 2 / 2
| 2

sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."

sparser
"UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46."
USP1 affects WDR48
| 5
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
WDR48 binds USP1 and USP46. 2 / 2
| 2

sparser
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."

sparser
"Also, UAF1 can interact with USP1 and USP46 in addition to USP12 [ xref ]."
USP1 affects USP12
| 5
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
USP1 binds USP12 and USP46. 2 / 2
| 2

sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."

sparser
"UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46."
Particulate Matter decreases the amount of USP46.
3 |
Particulate Matter decreases the amount of USP46. 3 / 3
3 |

No evidence text available

No evidence text available

No evidence text available
Particulate Matter increases the amount of USP46.
2 |
Particulate Matter increases the amount of USP46. 2 / 2
2 |

No evidence text available

No evidence text available
ILC3 affects USP46
| 5
USP46 binds ILC3. 5 / 5
| 5

sparser
"Additionally, ILC3USP46 enriched immune‐regulation‐related GO terms, such as ‘immune response‐activating cell surface receptor signalling’, ‘positive regulation of interferon‐gamma production’, ‘lymphocyte differentiation’, indicating its proinflammatory function."

sparser
"In the other branch, ILC3‐CCR7 cells progress through intermediate states, including ILC3USP46 and ILC3‐GNLY, towards transcriptional profiles resembling ILC1/NK cells (Figure  xref )."

sparser
"Intriguingly, unlike ILC3‐CCR7, which is enriched in the normal intestine, the other three subsets of ILC3s (ILC3USP46, ILC3‐GNLY and ILC3‐HSPA1B) are primarily distributed in CRC."

sparser
"Unsupervised clustering further identified four transcriptionally distinct subgroups, namely ILC3‐CCR7, ILC3‐HSPA1B, ILC3USP46 and ILC3‐GNLY (Figures  xref and xref )."

sparser
"ILC3USP46 displayed elevated expression of genes involved in cell adhesion and migration (e.g., SELL and CD38 ), and transcriptional regulation of immune responses (e.g., IRF8 )."
HYCC1 affects USP46
| 5
HYCC1 activates USP46. 5 / 5
| 5

reach
"When knocking down USP46, the proliferation activity of HCC cells was significantly enhanced, while it was significantly inhibited after over-expressing USP4."

reach
"Our research confirmed that USP46 regulates YAP1.To further demonstrate whether YAP1 inhibition was responsible for the tumor suppressor functions of USP46 in HCC, we transfected a YAP1 overexpression[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Importantly, ectopic expression of YAP1 abolished the reduced proliferation and invasion phenotypes in USP46-overexpressing HCC cells, indicating that USP46 exerts its function by regulating YAP1."

reach
"Inhibition of MST1 rescued YAP1 protein expression in USP46-overexpressing HCC cells."

reach
"In addition, upregulation of YAP1 promoted lung metastasis in USP46-overexpressing HCC cells ( Fig. 4 H)."
Δ affects USP46
| 4
Δ phosphorylates USP46.
| 2
Δ phosphorylates USP46. 2 / 2
| 2

reach
"As shown in Supplementary Fig. 9c, CK1δ significantly increased the phosphorylation of USP46 WT assessed by anti-p-Ser and anti-p-Thr antibodies, whereas the 3A mutant could largely decrease such phosphorylation events."

reach
"We next investigated whether CK1δ could phosphorylate USP46."
Δ binds USP46.
| 2
Δ binds USP46. 2 / 2
| 2

reach
"In addition, purified GST-CK1δ protein could pull-down His-USP46 in a cell-free system, indicating the direct interaction between CK1δ and USP46 (Fig. 6c)."

reach
"Second, CK1δ binds and regulates the phosphorylation of USP46 (Fig. 6 and Supplementary Fig. 9)."
Bisphenol A affects USP46
4 |
Bisphenol A increases the amount of USP46.
2 |
Bisphenol A increases the amount of USP46. 2 / 2
2 |

No evidence text available

No evidence text available
Bisphenol A methylates USP46.
1 |
1 |

No evidence text available
Bisphenol A decreases the amount of USP46.
1 |
Bisphenol A decreases the amount of USP46. 1 / 1
1 |

No evidence text available
| 1 3
USP46 translocates to the cytosol. 2 / 2
| 1 1

sparser
"The researchers used a systematic and unbiased screening strategy to uncover DUBs that participate in TCR signaling in primary T cells under physiological settings, and captured USP12 and USP46 that a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The researchers used a systematic and unbiased screening strategy to uncover DUBs that participate in TCR signaling in primary T cells under physiological settings, and captured USP12 and USP46 that a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 translocates to the nucleus. 1 / 1
| 1

sparser
"We could not determine whether the E6 translocated USP46 to the nucleus of the cancer cells, because contrary to the well-known cytoplasmic localization of USP46 in cell lines in culture, IHC with the USP46 antibody revealed that USP46 is nuclear in both normal and malignant areas of cervical squamous epithelium ( xref )."
USP46 translocates to the plasma membrane. 1 / 1
| 1

sparser
"On the other hand, since YFP-USP46 was not recruited to the PM, but accumulated in the cytoplasm when co-expressed with Myc-WDR20 (see Fig. 2 b), we tested the role of WDR20 NES on the localization of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects SNX5
| 2 2
USP46 binds SNX5.
| 1 2
| 1 2

sparser
"Heliox alleviates ischemia-reperfusion-induced damage to neuronal cells by repressing the USP46-SNX5 Axis-triggered ferroptosis."

sparser
"These observations highlight the ferroptosis-promoting function of the USP46-SNX5 axis in I/R-treated neuronal cells."

reach
"USP46 interacts with and deubiquitinates SNX5, a ferroptosis promoter, thereby increasing its stability."
USP46 deubiquitinates SNX5.
| 1
USP46 deubiquitinates SNX5. 1 / 1
| 1

reach
"USP46 interacts with and deubiquitinates SNX5, a ferroptosis promoter, thereby increasing its stability."
USP46 affects RAD51AP1
4 |

No evidence text available

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USP46 affects PLPP3
| 4
| 4

sparser
"When USP46 and PLPP3 interact, the split Venus fragments reconstitute into a functional fluorescent protein, which leads to the appearance of fluorescence."

sparser
"These findings suggest that USP46 interacts with PLPP3 at the plasma membrane."

sparser
"Next, we investigated the subcellular localization of the interaction between USP46 and PLPP3."

sparser
"Localization of the interaction between USP46 and PLPP3."
USP46 affects PGAM1
3 | 1
USP46 binds PGAM1.
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP46 activates PGAM1.
| 1
USP46 activates PGAM1. 1 / 1
| 1

reach
"Mechanistically, USP46 enhanced the protein stability of phosphoglycerate mutase 1 (PGAM1) via direct interaction."
USP46 affects Histone
| 4
USP46 deubiquitinates Histone-H2A. 4 / 4
| 4

reach
"Joo et al. demonstrated that USP46 and USP12 containing fractions from HeLa cells can deubiquitinate histones H2A and H2B to control cell fate and gastrulation during Xenopus development [XREF_BIBR]."

reach
"Several DUBs have been implicated in histone deubiquitination, including USP3, USP12, USP22, and USP46, which deubiquitinate both histones H2A and histones H2B [XREF_BIBR]."

reach
"In other species, USP46 deubiquitinates deubiquitinate histones H2A and H2B associated to USP12 and WDR48 proteins, reinforcing its epigenetic function [40]."

reach
"USP12 and USP46 can deubiquitinate histones H2A and H2B, thereby playing a critical role in Xenopus development [91] ."
USP46 affects DEPDC5
| 4
| 4

sparser
"To further validate the interaction between DEPDC5 and USP46, we performed co-immunoprecipitation between DEPDC5 and USP46 from cytosolic fractions and the proximity ligation assay (PLA)."

sparser
"Taken together, the results indicate that, in addition to the USP46-DEPDC5 interactions, mTORC1 hyperactivity is necessary to increase the excitatory synaptic strength."

sparser
"The number of PLA-positive puncta between DEPDC5 and USP46 was significantly higher than those observed in the negative control and comparable with the number of puncta observed in the βIII-tubulin/MAP2 positive control, confirming the interaction between DEPDC5 and USP46 ( xref C)."

sparser
"Notwithstanding the direct interaction between Depdc5 and USP46, the observed increase in the excitatory synaptic strength in Depdc5 cKO neurons is not independent of mTORC1 hyperactivity."
USP46 affects CASP3
| 4
USP46 decreases the amount of CASP3.
| 2
USP46 decreases the amount of CASP3. 2 / 2
| 2

reach
"As shown in Supplementary Fig. 6f, the reconstitution of USP46 WT but not the inactive C44S mutant could rescue the alterations of Ki67 and cleaved caspase-3 expression caused by the depletion of USP46."

reach
"The present experimental results demonstrated that the knockdown of USP46 upregulated Bcl-2 expression levels and downregulated the expression levels of Bax, caspase-3 and caspase-9."
USP46 increases the amount of CASP3.
| 1
USP46 increases the amount of CASP3. 1 / 1
| 1

reach
"The present experimental results demonstrated that the knockdown of USP46 upregulated Bcl-2 expression levels and downregulated the expression levels of Bax, caspase-3 and caspase-9."
USP46 activates CASP3.
| 1
USP46 activates CASP3. 1 / 1
| 1

reach
"USP46 activates the Bcl-2 and caspase-3 apoptotic signaling pathway and inactivates AKT activity."
RAD51AP1 affects USP46
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
PLPP3 affects USP46
| 4
| 4

sparser
"When USP46 and PLPP3 interact, the split Venus fragments reconstitute into a functional fluorescent protein, which leads to the appearance of fluorescence."

sparser
"These findings suggest that USP46 interacts with PLPP3 at the plasma membrane."

sparser
"Next, we investigated the subcellular localization of the interaction between USP46 and PLPP3."

sparser
"Localization of the interaction between USP46 and PLPP3."
DEPDC5 affects USP46
| 4
| 4

sparser
"To further validate the interaction between DEPDC5 and USP46, we performed co-immunoprecipitation between DEPDC5 and USP46 from cytosolic fractions and the proximity ligation assay (PLA)."

sparser
"Taken together, the results indicate that, in addition to the USP46-DEPDC5 interactions, mTORC1 hyperactivity is necessary to increase the excitatory synaptic strength."

sparser
"The number of PLA-positive puncta between DEPDC5 and USP46 was significantly higher than those observed in the negative control and comparable with the number of puncta observed in the βIII-tubulin/MAP2 positive control, confirming the interaction between DEPDC5 and USP46 ( xref C)."

sparser
"Notwithstanding the direct interaction between Depdc5 and USP46, the observed increase in the excitatory synaptic strength in Depdc5 cKO neurons is not independent of mTORC1 hyperactivity."
4 |
Air Pollutants increases the amount of USP46.
2 |
Air Pollutants increases the amount of USP46. 2 / 2
2 |

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Air Pollutants decreases the amount of USP46.
2 |
Air Pollutants decreases the amount of USP46. 2 / 2
2 |

No evidence text available

No evidence text available
3 |
Valproic acid decreases the amount of USP46. 3 / 3
3 |

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No evidence text available
Rotenone affects USP46
3 |
Rotenone increases the amount of USP46. 3 / 3
3 |

No evidence text available

No evidence text available

No evidence text available
Wnt affects USP46
| 3
Wnt activates USP46. 3 / 3
| 3

reach
"Wnt signaling promotes the binding of the USP46 complex to the Wnt coreceptor LRP6 at the cell surface, stabilizing LRP6 on the cell surface."

reach
"Wnt signaling induces the assembly of USP46, UAF1, and WDR20 into large cytoplasmic complexes but not into LRP6 signalosomes."

reach
"Thus, Wnt signaling induced a physical alteration of the USP46 complex in the cytoplasm.Because the association of the USP46 complex with LRP6 was enhanced in the presence of Wnt stimulation (Fig. 3E, F), we tested whether the USP46 complex interacted with LRP6 receptor aggregates in signalosomes that could be readily detected in sucrose density gradients ."
WDR20 affects USP12
| 3
| 2

sparser
"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [ xref , xref ]."

sparser
"Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
WDR proteins affects USP46
| 3
WDR proteins binds USP46. 3 / 3
| 3

reach
"Together, these structural studies suggest that binding of the WDR proteins to USP12 or USP46 relatively far from the active site results in the rearrangement of several structural elements, which propagates to the catalytic triad increasing enzyme catalysis."

reach
"Biochemical and proteomic studies showed that two WDR proteins, WDR48 (also known as USP1 associated factor, UAF1) and WDR20, interact with USP46 and USP12."

reach
"We highlight recent structural insights into how WDR proteins interact with and regulate USP46, and discuss functions for the USP46 and WDR protein complex in the nervous system and across phylogeny."

reach
"Functionally, USP46 promotes ESCC metastasis in vitro and in vivo by inducing the EMT process."

reach
"Besides, USP46 promotes ESCC metastasis by regulating EMT process and has an effect of inhibiting ubiquitination of ENO1 protein."

reach
"Collectively, these results displayed that USP46 enhances the metastatic capacity of ESCC cells through inducing the process of EMT in a catalytic-dependent way.Given that USP46 promotes ESCC cell met[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects WDR proteins
| 3
WDR proteins binds USP46. 3 / 3
| 3

reach
"Together, these structural studies suggest that binding of the WDR proteins to USP12 or USP46 relatively far from the active site results in the rearrangement of several structural elements, which propagates to the catalytic triad increasing enzyme catalysis."

reach
"Biochemical and proteomic studies showed that two WDR proteins, WDR48 (also known as USP1 associated factor, UAF1) and WDR20, interact with USP46 and USP12."

reach
"We highlight recent structural insights into how WDR proteins interact with and regulate USP46, and discuss functions for the USP46 and WDR protein complex in the nervous system and across phylogeny."
USP46 affects SNX6
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP46 affects SNX2
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP46 affects PTBP1
| 3
USP46 inhibits PTBP1.
| 1
USP46 inhibits PTBP1. 1 / 1
| 1

reach
"Knockdown of USP46 induced downregulation of PTBP1 protein by promoting its K48-linked ubiquitination, resulting in a decreased PKM2/PKM1 ratio, reduced glycolysis, and heightened TAM sensitivity in BC cells."
USP46 increases the amount of PTBP1.
| 1
USP46 increases the amount of PTBP1. 1 / 1
| 1

reach
"In particular, USP46 collaborates with PTBP1 to raise the protein levels of PTBP1, which in turn increase the PKM2/PKM1 ratio, improves glycolysis, and encourages BC cells to become resistant to tamoxifen."
USP46 activates PTBP1.
| 1
USP46 activates PTBP1. 1 / 1
| 1

reach
"USP46 enhances tamoxifen resistance in breast cancer cells by stabilizing PTBP1 to facilitate glycolysis."
USP46 affects IFI30
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP46 affects GST
| 3
| 3

sparser
"In addition, a significant decrease of polyubiquitinated NRAS Q61R was observed when incubated with purified GST-USP46 WT rather than the C44S mutant in vitro (Fig. xref )."

sparser
"As shown in Fig. xref , purified GST-USP46 interacted with the NRAS Q61R and NRAS Q61K mutant more strongly than NRAS WT and Q61L. We also modeled the structure of ubiquitinated NRAS in complex with USP46 using protein-protein docking (Schrödinger, LLC, New York, NY, 2023) based on the USP46-UB complex structure (PDB ID: 5CVM) and NRAS Q61K (PDB ID: 8VM2)."

sparser
"Additionally, purified GST-USP46 interacted with the NRAS Q61R mutant much more strongly than KRAS WT, HRAS WT and their mutants (Supplementary Fig.  xref )."
USP46 affects GRIA2
| 3
USP46 deubiquitinates GRIA2.
| 2
USP46 deubiquitinates GRIA2. 2 / 2
| 2

reach
"We observed that USP46 is able to deubiquitinate not only GluA1 but also GluA2, indicating a relative stringency in contrast to the distinct E3 ligases that are employed for GluA1 and GluA2."

reach
"Mammalian USP46 can deubiquitinate both GluA1 and GluA2 subunits and protect AMPARs from degradation."
USP46 ubiquitinates GRIA2.
| 1
USP46 ubiquitinates GRIA2. 1 / 1
| 1

reach
"By deubiquitinating K63 ubiquitinated glutaminergic AMPARs (α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid) receptors GluA1 and GluA2, which are considered to mediate most of the excitatory synaptic transmission in the brain, USP46 upregulates the intracellular trafficking, cell surface density, and signal intensity of AMPARs [116,117]."
USP46 affects CK1δ
| 3
CK1δ binds USP46. 3 / 3
| 3

sparser
"CK1δ binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."

sparser
"In addition, purified GST-CK1δ protein could pull-down His-USP46 in a cell-free system, indicating the direct interaction between CK1δ and USP46 (Fig. xref )."

sparser
"The endogenous USP46-CK1δ interaction were validated in SK-MEL-103 and SK-MEL-30 cells, respectively (Fig. xref and Supplementary Fig.  xref )."
USP46 affects CIRBP
1 | 2
1 | 2

No evidence text available

sparser
"Immunoprecipitation experiments showed that USP46 interacts with CIRBP to inhibit its ubiquitination."

sparser
"USP46 interacts with CIRBP to reduce its ubiquitination and stabilize its expression, thereby promoting ferroptosis."
USP46 affects BCL2
| 3
USP46 decreases the amount of BCL2.
| 2
USP46 decreases the amount of BCL2. 2 / 2
| 2

reach
"The present experimental results demonstrated that the knockdown of USP46 upregulated Bcl-2 expression levels and downregulated the expression levels of Bax, caspase-3 and caspase-9."

reach
"The results indicated that decreased USP46 expression led to an increase in the levels of the anti-apoptotic protein Bcl-2, while there was a corresponding decrease in key pro-apoptotic proteins such as caspase-3, caspase-9, and Bax."
USP46 activates BCL2.
| 1
USP46 activates BCL2. 1 / 1
| 1

reach
"USP46 activates the Bcl-2 and caspase-3 apoptotic signaling pathway and inactivates AKT activity."
USP46 affects BAX
| 3
USP46 inhibits BAX.
| 1
USP46 inhibits BAX. 1 / 1
| 1

reach
"Furthermore, reduced expression of USP46 contributes to cisplatin resistance by suppressing the apoptotic mediators Caspase3, Bax, and poly‑ADP ribose polymerase (PARP), while concurrently activating BCL2."
USP46 increases the amount of BAX.
| 1
USP46 increases the amount of BAX. 1 / 1
| 1

reach
"The present experimental results demonstrated that the knockdown of USP46 upregulated Bcl-2 expression levels and downregulated the expression levels of Bax, caspase-3 and caspase-9."
USP46 decreases the amount of BAX.
| 1
USP46 decreases the amount of BAX. 1 / 1
| 1

reach
"The present experimental results demonstrated that the knockdown of USP46 upregulated Bcl-2 expression levels and downregulated the expression levels of Bax, caspase-3 and caspase-9."
USP12 affects WDR20
| 3
| 2

sparser
"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [ xref , xref ]."

sparser
"Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1."
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
USP1 affects USP12, USP46, and WDR48
| 3
| 3

sparser
"UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity."

sparser
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity ( xref ; xref )."

sparser
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1-associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [ xref ]."
SNX6 affects USP46
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No evidence text available

No evidence text available
SNX5 affects USP46
| 1 2
| 1 2

sparser
"Heliox alleviates ischemia-reperfusion-induced damage to neuronal cells by repressing the USP46-SNX5 Axis-triggered ferroptosis."

sparser
"These observations highlight the ferroptosis-promoting function of the USP46-SNX5 axis in I/R-treated neuronal cells."

reach
"USP46 interacts with and deubiquitinates SNX5, a ferroptosis promoter, thereby increasing its stability."
SNX2 affects USP46
3 |
3 |

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No evidence text available

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PGAM1 affects USP46
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
IFI30 affects USP46
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
GST affects USP46
| 3
| 3

sparser
"In addition, a significant decrease of polyubiquitinated NRAS Q61R was observed when incubated with purified GST-USP46 WT rather than the C44S mutant in vitro (Fig. xref )."

sparser
"As shown in Fig. xref , purified GST-USP46 interacted with the NRAS Q61R and NRAS Q61K mutant more strongly than NRAS WT and Q61L. We also modeled the structure of ubiquitinated NRAS in complex with USP46 using protein-protein docking (Schrödinger, LLC, New York, NY, 2023) based on the USP46-UB complex structure (PDB ID: 5CVM) and NRAS Q61K (PDB ID: 8VM2)."

sparser
"Additionally, purified GST-USP46 interacted with the NRAS Q61R mutant much more strongly than KRAS WT, HRAS WT and their mutants (Supplementary Fig.  xref )."
EBNA3 affects USP46
| 2 1
EBNA3 binds USP46.
| 1 1
| 1 1

sparser
"They found that EBNA3 proteins can interact with USP46 deubiquitinating enzyme (DUB) as well as its associated chaperones WDR48 and WDR20 [ xref ]."

reach
"EBNA3A can bind to RBPJ, a Notch pathway protein, and USP46/USP12 or CtBP ."
EBNA3 activates USP46.
| 1
EBNA3 activates USP46. 1 / 1
| 1

reach
"Because we did not find peptides corresponding to other EBNA proteins in these complexes, each EBNA3 protein appears to target RBPJ and the USP46 and USP12 DUB complexes independently."
E6 affects DTL
| 3
E6 binds USP46 and DTL. 3 / 3
| 3

sparser
"The elution profile also suggests that the Cdt2 associates with E6-USP46, as a low-affinity substoichiometric substrate rather than as a core member of the E6-USP46 complex."

sparser
"In Hela cells, E6 is associates with E6AP and p53, and now we find that the E6 protein also associates with USP46 and Cdt2."

sparser
"We propose that the E6-USP46 interaction promotes the tripartite E6-USP46-Cdt2 complex either due to allosteric changes in USP46, or because Cdt2 interacts simultaneously with sites on E6 and USP46 ( xref )."
CIRBP affects USP46
1 | 2
1 | 2

No evidence text available

sparser
"Immunoprecipitation experiments showed that USP46 interacts with CIRBP to inhibit its ubiquitination."

sparser
"USP46 interacts with CIRBP to reduce its ubiquitination and stabilize its expression, thereby promoting ferroptosis."
AKT affects USP46
| 2 1
AKT activates USP46.
| 2
AKT activates USP46. 2 / 2
| 2

reach
"To further validate if AKT mediates USP46 function in RCC, we detected AKT pathway activity in the USP46 depleted cells in the presence of a selective inhibitor (MK2206)."

reach
"We tested if AKT-specific inhibitor can block the function in USP46 knockdown cells."
AKT binds USP46.
| 1
| 1

sparser
"As previously described, USP46 mediated PHLPP stability in colon cancer through AKT inaction, indicating a novel mechanism of the USP46-AKT axis in tumor regulation."
2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP46.
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2 |

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2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP46.
1 |
1 |

No evidence text available
Propeller affects USP46
| 2
| 2

reach
"In this in vitro setting, a construct consisting of only the WDR48 beta propeller (27-359) was able to stimulate USP46 almost as well as the full-length WT WDR48 construct, again corroborating the imp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Given the distinct binding mode elucidated here, it is less straightforward to reconcile this structure with direct active-site modulation, yet we propose a mechanism centered on WDR48 dependent USP s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Muscimol affects USP46
| 2
Muscimol inhibits mutated USP46. 2 / 2
| 2

reach
"The muscimol induced current in the hippocampal CA1 pyramidal neurons and hippocampal expression of the 67-kDa isoform of glutamic acid decarboxylase were significantly decreased in the Usp46 mutant mice compared to control mice."

reach
"The muscimol induced current in the hippocampal CA1 pyramidal neurons and hippocampal expression of the 67-kDa isoform of glutamic acid decarboxylase significantly decreased in the Usp46 mutant mice compared to control mice."
MiR-27a-3p affects USP46
| 2
MiR-27a-3p inhibits USP46.
| 1
MiR-27a-3p inhibits USP46. 1 / 1
| 1

reach
"However, another experiment has revealed that miR-27a-3p down-regulates USP46 in decreasing growth rate of hepatocellular carcinoma cells ( Wen et al., 2022 )."
MiR-27a-3p increases the amount of USP46.
| 1
MiR-27a-3p increases the amount of USP46. 1 / 1
| 1

reach
"For instance, miR-27a-3p overexpression in the liver enhances cancer cell proliferation by inhibiting USP46 expression [44]."
2 |
Hsa-miR-873-5p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-6893-3p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-6765-3p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-5585-5p decreases the amount of USP46. 2 / 2
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No evidence text available
2 |
Hsa-miR-548ax decreases the amount of USP46. 2 / 2
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No evidence text available
2 |
Hsa-miR-548ao-5p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-4797-5p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-4722-5p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-370-3p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-3622b-3p decreases the amount of USP46. 2 / 2
2 |

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No evidence text available
2 |
Hsa-miR-3622a-3p decreases the amount of USP46. 2 / 2
2 |

No evidence text available

No evidence text available

reach
"Therefore, in the present study, we examined whether the immobility time is influenced by drugs affecting the action mediated by GABA A receptor using both 3-bp deleted (the Usp46 mutant) and null Usp46 (Usp46 KO) mice."
| 1

reach
"Therefore, in the present study, we examined whether the immobility time is influenced by drugs affecting the action mediated by GABA A receptor using both 3-bp deleted (the Usp46 mutant) and null Usp46 (Usp46 KO) mice."
All-trans-retinoic acid increases the amount of USP46.
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All-trans-retinoic acid increases the amount of USP46. 1 / 1
1 |

No evidence text available
All-trans-retinoic acid decreases the amount of USP46.
1 |
All-trans-retinoic acid decreases the amount of USP46. 1 / 1
1 |

No evidence text available
2 |
Aflatoxin B1 methylates USP46.
1 |
1 |

No evidence text available
Aflatoxin B1 demethylates USP46.
1 |
Aflatoxin B1 demethylates USP46. 1 / 1
1 |

No evidence text available
YAP1 affects USP46
| 2
| 2

sparser
"Importantly, the co-IP assay showed that USP46 does not directly interact with YAP1 but interacts with MST1 in HCC cells."

sparser
"However, our immunoprecipitation results demonstrated that there was no direct interaction between USP46 and YAP1 ( Supplementary Fig. S2 E )."
USP46 affects δ
| 2
Δ binds USP46. 2 / 2
| 2

reach
"In addition, purified GST-CK1δ protein could pull-down His-USP46 in a cell-free system, indicating the direct interaction between CK1δ and USP46 (Fig. 6c)."

reach
"Second, CK1δ binds and regulates the phosphorylation of USP46 (Fig. 6 and Supplementary Fig. 9)."
USP46 affects mHTT
| 2
USP46 inhibits mHTT. 2 / 2
| 2

reach
"When transfected at a similar gene dose as that at which Usp12 rescues mHTT toxicity, Usp46 did not block degeneration of mHTT expressing neurons."

reach
"The neuroprotective role of Usp12 may be specific amongst related deubiquitinases, as the closely related homolog Usp46 does not suppress mHTT mediated toxicity."

reach
"Importantly, USP46 stimulated the glycolysis and promoted the malignant growth of TNBC cells through upregulation of PGAM1."

reach
"We observed that knockdown of USP46 led to decreased HIF-1α levels and reduction in glycolysis rate, thereby attenuating myocardial hypertrophy in mice model of cardiac hypertrophy."
USP46 affects cisplatin
| 2
| 2

reach
"https://doi.org/10.3892/mmr.2021.12024.The images for Figure 4A, sh-LINC01260 and sh-Control have been duplicated with the images for Figure 3A, NC and miR-613 mimics, respectively, from Luo et al, 2021.Images for Figure 4F have been duplicated with images for Figure 1D from Xu L, Zhang B, Li W. Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2."

reach
"[Retracted] Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2."
| 2
USP46 inhibits cell migration.
| 1

reach
"As shown in Fig. 3 A and B, upregulation of USP46 inhibited Huh-7 cell migration and invasion abilities in vitro ."
USP46 activates cell migration.
| 1

reach
"Our studies illustrated that USP46 could strikingly promote cell migration, invasion and tumor metastasis of ESCC."
USP46 affects cell growth
| 2
USP46 inhibits cell growth.
| 1
| 1

reach
"To determine whether USP46 mediated cell growth and migration inhibition resulting from AKT signaling pathway inhibition, we analyzed the AKT and downstream S6K1 activation in the USP46 overexpression[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 activates cell growth.
| 1
| 1

reach
"To determine whether USP46 mediated cell growth and migration inhibition resulting from AKT signaling pathway inhibition, we analyzed the AKT and downstream S6K1 activation in the USP46 overexpression[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects XRCC1
| 2
USP46 inhibits XRCC1. 2 / 2
| 2

reach
"Our data indicate that USP46 represses RCC tumor progression via the inhibition of the AKT signaling pathway."

reach
"We described a new mechanism by which USP46 inhibits RCC survival via the downregulation of the AKT signaling pathway."
USP46 affects Wnt
| 2
USP46 deubiquitinates Wnt.
| 1
USP46 leads to the deubiquitination of Wnt. 1 / 1
| 1

reach
"The USP46 complex blocks ubiquitylation/degradation of the Wnt co-receptor LRP6 [33]."
USP46 activates Wnt.
| 1
USP46 activates Wnt. 1 / 1
| 1

reach
"The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6."
USP46 affects USP
| 2
USP46 activates USP. 2 / 2
| 2

reach
"It raises the possibility that a targeted knockout of Uaf1 in granulosa cells might lead to infertility in female mice, which could provide further insights into UAF1’s specific functions in female reproductive biology.UAF1 acts as a cofactor for USP1, USP12, and USP46, enhancing their deubiquitinase activity by forming stable UAF1/USP protein complexes.14 18 Defective spermiogenesis in Uaf1 sKO mice necessitated the identification of a DUB critical for this process."

reach
"These results indicated that UAF1 suppressed JEV replication.As the cofactor of USP1, USP12, and USP46, UAF1 could enhance their deubiquitinase activity by forming stable UAF1/USP protein complexes (6, 38)."
USP46 affects TSPYL6
2 |
2 |

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No evidence text available
USP46 affects TRAF6
| 1 1
| 1 1

reach
"Co-immunoprecipitation experiments demonstrated a direct interaction between USP46 and TRAF6, implicating USP46 in the modulation of TRAF6 ubiquitination, a process that is fundamental to tumor physiology."

sparser
"Co-immunoprecipitation experiments demonstrated a direct interaction between USP46 and TRAF6, implicating USP46 in the modulation of TRAF6 ubiquitination, a process that is fundamental to tumor physiology."
USP46 affects THUMPD3
2 |
2 |

No evidence text available

No evidence text available
USP46 affects TBK1
| 1 1
USP46 deubiquitinates TBK1.
| 1
USP46 deubiquitinates TBK1. 1 / 1
| 1

reach
"USP46 promotes the interferon antiviral signaling in black carp by deubiquitinating TBK1."
USP46 binds TBK1.
| 1
USP12 binds USP46 and TBK1. 1 / 1
| 1

sparser
"In addition, USP12 and USP46 were not associated with TBK1 ( xref )."
USP46 affects SUCLG2
| 2

sparser
"Lower expression of FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 were associated with advanced tumor stage (Figure xref A); lower expression of RAP2C-AS1 was related to lymphatic invasion (Figure xref B); lower expression of RAP2C-AS1, USP46-AS1, AC112220.2 and AC015922.2 tended to promote tumor metastasis (Figure xref C); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 expression levels were correlated with higher pathological stage (Figure xref D); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2 and AC015922.2 expression levels were also correlated with higher histological grade (Figure xref E)."

sparser
"In this study, we found that several lncRNAs, including FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, ENSG00000271020, AC112220.2, AC018647.2, AC015922.2, MID1IP1-AS1, AL731577.2 and AL450326.1 were co-expressed with VHL, and their expression were positively correlated with VHL expression."
USP46 affects RNF43
| 2
USP46 inhibits RNF43. 2 / 2
| 2

reach
"In contrast, overexpression of the USP46 complex blocks ubiquitylation of LRP6 by the ubiquitin ligases RNF43 and ZNFR3."

reach
"Because the USP46 complex opposes the action of RNF43 and ZNRF3, loss of USP46 would be expected to potentiate the activities of RNF43 and ZNRF3, decreasing the effectiveness of RSPO in maintaining intestinal organoid growth."
USP46 affects RNF19B
2 |
2 |

No evidence text available

No evidence text available
USP46 affects Phosphatase
| 1 1

sparser
"USP46 interacts with PH domain leucine-rich repeat protein phosphatase (PHLPP) and controls its expression via deubiquitination."

reach
"USP46 interacts with PH domain leucine-rich repeat protein phosphatase (PHLPP) and controls its expression via deubiquitination."
USP46 affects PPM1B
| 2
USP46 increases the amount of PPM1B.
| 1
USP46 increases the amount of PPM1B. 1 / 1
| 1

reach
"We found that USP46 could be co-immunoprecipitated with PPM1B (Supplementary Fig. 3f) and that USP46 overexpression increased levels of PPM1B protein to some extent (Supplementary Fig. 3g), whereas silencing USP46 resulted in a slight decrease in PPM1B expression (Supplementary Fig. 3h)."
USP46 deubiquitinates PPM1B.
| 1
USP46 deubiquitinates PPM1B. 1 / 1
| 1

reach
"Yang et al. found that USP12 and USP46 deubiquitinates and stabilizes PPM1B to regulate chemokine production in tumor cells ( Yang et al., 2021 )."
USP46 affects KIF2A
| 1 1
| 1 1

sparser
"We also found that USP46KIF2A complex forms nuclear puncta (Fig.  xref )."

reach
"We also found that USP46KIF2A complex forms nuclear puncta (Fig. 5B)."
USP46 affects IL17RB
| 2
USP46 binds DTL and IL17RB. 1 / 1
| 1

sparser
"Immunoprecipitates of myc-USP46 contained Cdt2 and DDB1 indicating that USP46 associates with CRL4-Cdt2 complex ( xref )."
| 1

sparser
"Interestingly, the USP46-CRL4 Cdt2 interaction also has implications for genome integrity as it regulates DNA repair proteins, including the TLS polη, dependent on its interaction with PCNA [ xref ]."
USP46 affects HSPA8
2 |
2 |

No evidence text available

No evidence text available
USP46 affects HOOK3
| 1 1
| 1 1

sparser
"The USP46HOOK3 complex was observed as a perinuclear condensate and was co‐localized with γ‐tubulin, a centrosome marker protein (Fig.  xref )."

reach
"The USP46HOOK3 complex was observed as a perinuclear condensate and was co‐localized with γ‐tubulin, a centrosome marker protein (Fig. 5B,C)."
USP46 affects H2BC21
1 1 |
USP46 deubiquitinates H2BC21.
1 |
USP46 deubiquitinates H2BC21. 1 / 1
1 |

"Regulation of histone H2A and <span class="match term1">H2B</span> deubiquitination and Xenopus development by USP12 and <span class="match term0">USP46</span>"
USP46 binds H2BC21.
1 |
1 |

No evidence text available
USP46 affects H2AC20
1 1 |
USP46 deubiquitinates H2AC20.
1 |
USP46 deubiquitinates H2AC20. 1 / 1
1 |

"Regulation of histone <span class="match term1">H2A</span> and H2B deubiquitination and Xenopus development by USP12 and <span class="match term0">USP46</span>"
USP46 binds H2AC20.
1 |
1 |

No evidence text available
USP46 affects GORASP1
2 |
2 |

No evidence text available

No evidence text available
USP46 affects Flag
| 2
| 2

sparser
"We transiently transfected the USP46-Flag plasmids into HEK293T cells, and then performed LC-MS/MS analysis to investigate the whole proteins that could be co-immunoprecipitated with USP46 ( Fig. 5 A)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"USP46-Flag plasmids or empty vectors were transfected into HEK293T cells for 24 h respectively and then we performed the co-immunoprecipitation assay."

reach
"In addition to affecting the proliferation of cancer cells, USP46 has also been demonstrated to promote tumor metastasis by stabilizing ENO1 in human esophageal squamous cell carcinoma [ 28 ]."

reach
"However, in esophageal squamous cell carcinoma and cervical cancer (CC), USP46 increases tumor growth."
USP46 affects ERK
| 2
USP46 increases the amount of phosphorylated ERK. 2 / 2
| 2

reach
"As shown in Fig. 7j and Supplementary Fig. 10g, the overexpression of USP46 WT, but not the 3 A mutant in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly increased the protein level of NRAS mutants and levels of p-AKT and p-ERK."

reach
"Furthermore, the depletion of USP46 in SK-MEL-103, SK-MEL-30 and SK-MEL-2 cells significantly suppressed levels of p-AKT and p-ERK, cellular proliferation, migration and invasion abilities along with increased cellular sensitivity to DTIC, whereas the reconstitution of NRAS Q61R/K, NRAS Q61R-K135R + K147R or NRAS Q61R-K135R + K147L in USP46-deficient cells markedly rescue such effects (Fig. 5i–l and Supplementary Figs."
USP46 affects EBNA3
| 1 1
| 1 1

sparser
"They found that EBNA3 proteins can interact with USP46 deubiquitinating enzyme (DUB) as well as its associated chaperones WDR48 and WDR20 [ xref ]."

reach
"EBNA3A can bind to RBPJ, a Notch pathway protein, and USP46/USP12 or CtBP ."
USP46 affects E1
1 1 |
1 1 |

No evidence text available

No evidence text available
| 1 1
| 1 1

eidos
"In SKOV3 / DDP cells , the upregulation of USP46 expression levels notably suppressed cell viability and increased cell apoptosis ."

reach
"In SKOV3 and DDP cells, the upregulation of USP46 expression levels notably suppressed cell viability and increased cell apoptosis."

reach
"MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma."

reach
"These experimental results indicate that USP46 inhibits the invasion and metastasis of hepatoma cells in vivo and in vitro ."
USP46 affects CTNNB1
| 2
USP46 inhibits CTNNB1.
| 1
USP46 inhibits CTNNB1. 1 / 1
| 1

reach
"Usp46 inactivation in Wingless-responding cells destabilizes Arrow, reduces cytoplasmic accumulation of the transcriptional coactivator Armadillo/beta-catenin, and attenuates or abolishes Wingless target gene activation, which prevents the concentration-dependent regulation of signaling strength."
USP46 increases the amount of CTNNB1.
| 1
USP46 increases the amount of CTNNB1. 1 / 1
| 1

reach
"We found that knockdown of USP46 decreased the viability of intestinal organoids and LRP6 and β-catenin levels (Fig. 5F and Supplementary Fig. 7A, B) and that this effect was more evident at lower concentrations of RSPO (corresponds to higher RNF43/ZNRF3 activities)."
USP46 affects CHRM3
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2 |

No evidence text available

No evidence text available
USP46 affects CCN2
| 2
USP46 decreases the amount of CCN2. 2 / 2
| 2

reach
"However, silencing USP46 markedly increased protein levels of both YAP1 and CTGF in HCC cells ( Fig. 4 A and B)."

reach
"As expected, western blotting results revealed that overexpression of USP46 significantly decreased YAP1 protein expression, as well as expression of CTGF, the target gene of YAP."
USP46 affects CASP9
| 2
USP46 increases the amount of CASP9.
| 1
USP46 increases the amount of CASP9. 1 / 1
| 1

reach
"The present experimental results demonstrated that the knockdown of USP46 upregulated Bcl-2 expression levels and downregulated the expression levels of Bax, caspase-3 and caspase-9."
USP46 decreases the amount of CASP9.
| 1
USP46 decreases the amount of CASP9. 1 / 1
| 1

reach
"The present experimental results demonstrated that the knockdown of USP46 upregulated Bcl-2 expression levels and downregulated the expression levels of Bax, caspase-3 and caspase-9."
USP46 affects AR
1 | 1
USP46 deubiquitinates AR. 2 / 2
1 | 1

reach
"Furthermore, overexpressed USP46 was able to deubiquitinate AR, similarly to our previous observations for USP12 [XREF_BIBR]."

"Here we report that the novel small molecule anti-androgen, galeterone targets USP12 and <span class="match term0">USP46</span>, two highly homologous deubiquitinating enzymes that control the <span class="match term1">AR</span>-AKT-MDM2-P53 signalling pathway."
USP46 affects ACTB
2 |
2 |

No evidence text available

No evidence text available
USP12 affects USP46, and WDR20
| 2
| 2

sparser
"WDR20 binding to USP12 and USP46 showed a significant increase in the catalytic activity in vitro [ xref , xref ]."

sparser
"Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1."
USP1 affects USP46, and WDR48
| 2
WDR48 binds USP1 and USP46. 2 / 2
| 2

sparser
"Homologous amino acid motifs, mapping to the Fingers sub-domain, mediate binding of USP1 and USP46 to UAF1."

sparser
"Also, UAF1 can interact with USP1 and USP46 in addition to USP12 [ xref ]."
USP1 affects USP12, and USP46
| 2
USP1 binds USP12 and USP46. 2 / 2
| 2

sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."

sparser
"UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46."
TSPYL6 affects USP46
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2 |

No evidence text available

No evidence text available
TRAF6 affects USP46
| 1 1
| 1 1

reach
"Co-immunoprecipitation experiments demonstrated a direct interaction between USP46 and TRAF6, implicating USP46 in the modulation of TRAF6 ubiquitination, a process that is fundamental to tumor physiology."

sparser
"Co-immunoprecipitation experiments demonstrated a direct interaction between USP46 and TRAF6, implicating USP46 in the modulation of TRAF6 ubiquitination, a process that is fundamental to tumor physiology."
THUMPD3 affects USP46
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2 |

No evidence text available

No evidence text available
TCF3 affects USP46
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TCF3 decreases the amount of USP46. 2 / 2
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No evidence text available

No evidence text available
SUCLG2 affects USP46
| 2

sparser
"Lower expression of FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 were associated with advanced tumor stage (Figure xref A); lower expression of RAP2C-AS1 was related to lymphatic invasion (Figure xref B); lower expression of RAP2C-AS1, USP46-AS1, AC112220.2 and AC015922.2 tended to promote tumor metastasis (Figure xref C); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 expression levels were correlated with higher pathological stage (Figure xref D); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2 and AC015922.2 expression levels were also correlated with higher histological grade (Figure xref E)."

sparser
"In this study, we found that several lncRNAs, including FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, ENSG00000271020, AC112220.2, AC018647.2, AC015922.2, MID1IP1-AS1, AL731577.2 and AL450326.1 were co-expressed with VHL, and their expression were positively correlated with VHL expression."
SPI1 affects USP46
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SPI1 decreases the amount of USP46. 2 / 2
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No evidence text available

No evidence text available
RNF19B affects USP46
2 |
2 |

No evidence text available

No evidence text available
Proteasome affects USP46
| 2
Proteasome inhibits USP46.
| 1
| 1

reach
"We found that increased expression of WDR-48, but not WDR-20, promotes USP-46 abundance in mammalian cells in culture and in C. elegans neurons in vivo Inhibition of the proteasome increased USP-46 abundance, and this effect was non additive with increased WDR-48 expression."
Proteasome activates USP46.
| 1
| 1

reach
"Increased USP46 prolonged the half-life of ENO1 by antagonizing ENO1 ubiquitination and inhibiting ENO1 proteasome-associated degradation."
Phosphatase affects USP46
| 1 1

sparser
"USP46 interacts with PH domain leucine-rich repeat protein phosphatase (PHLPP) and controls its expression via deubiquitination."

reach
"USP46 interacts with PH domain leucine-rich repeat protein phosphatase (PHLPP) and controls its expression via deubiquitination."
MIR1286 affects USP46
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MIR1286 decreases the amount of USP46. 2 / 2
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No evidence text available

No evidence text available
MIR1205 affects USP46
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MIR1205 decreases the amount of USP46. 2 / 2
2 |

No evidence text available

No evidence text available
KIF2A affects USP46
| 1 1
| 1 1

sparser
"We also found that USP46KIF2A complex forms nuclear puncta (Fig.  xref )."

reach
"We also found that USP46KIF2A complex forms nuclear puncta (Fig. 5B)."
IL17RB affects USP46
| 2
USP46 binds DTL and IL17RB. 1 / 1
| 1

sparser
"Immunoprecipitates of myc-USP46 contained Cdt2 and DDB1 indicating that USP46 associates with CRL4-Cdt2 complex ( xref )."
| 1

sparser
"Interestingly, the USP46-CRL4 Cdt2 interaction also has implications for genome integrity as it regulates DNA repair proteins, including the TLS polη, dependent on its interaction with PCNA [ xref ]."
HSPA8 affects USP46
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No evidence text available

No evidence text available
HOOK3 affects USP46
| 1 1
| 1 1

sparser
"The USP46HOOK3 complex was observed as a perinuclear condensate and was co‐localized with γ‐tubulin, a centrosome marker protein (Fig.  xref )."

reach
"The USP46HOOK3 complex was observed as a perinuclear condensate and was co‐localized with γ‐tubulin, a centrosome marker protein (Fig. 5B,C)."
GORASP1 affects USP46
2 |
2 |

No evidence text available

No evidence text available
Flag affects USP46
| 2
| 2

sparser
"We transiently transfected the USP46-Flag plasmids into HEK293T cells, and then performed LC-MS/MS analysis to investigate the whole proteins that could be co-immunoprecipitated with USP46 ( Fig. 5 A)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"USP46-Flag plasmids or empty vectors were transfected into HEK293T cells for 24 h respectively and then we performed the co-immunoprecipitation assay."
EBNA6 affects USP46
| 2
EBNA6 binds USP46.
| 1
| 1

reach
"EBNA3C interactions with RBPJ, CtBP, WDR48, and USP46 are also important for EBNA3C-mediated p16 repression [92,93,111] (Figure 1)."
EBNA6 activates USP46.
| 1
EBNA6 activates USP46. 1 / 1
| 1

reach
"Thus, EBNA3C also appears to target the USP46 complex; however, this complex appears to be less stably associated with EBNA3C-F-HA than it is with either EBNA3A-F-HA or EBNA3B-F-HA."
E1 affects USP46
1 1 |
1 1 |

No evidence text available

No evidence text available

sparser
"Lower expression of FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 were associated with advanced tumor stage (Figure xref A); lower expression of RAP2C-AS1 was related to lymphatic invasion (Figure xref B); lower expression of RAP2C-AS1, USP46-AS1, AC112220.2 and AC015922.2 tended to promote tumor metastasis (Figure xref C); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2, AC015922.2 and AL450326.1 expression levels were correlated with higher pathological stage (Figure xref D); lower FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, AC112220.2, AC018647.2 and AC015922.2 expression levels were also correlated with higher histological grade (Figure xref E)."

sparser
"In this study, we found that several lncRNAs, including FGD5-AS1, RAP2C-AS1, SUCLG2-AS1, USP46-AS1, AL391121.1, ENSG00000271020, AC112220.2, AC018647.2, AC015922.2, MID1IP1-AS1, AL731577.2 and AL450326.1 were co-expressed with VHL, and their expression were positively correlated with VHL expression."
CHRM3 affects USP46
2 |
2 |

No evidence text available

No evidence text available
ACTB affects USP46
2 |
2 |

No evidence text available

No evidence text available
ΔK92 affects USP46
| 1
ΔK92 binds USP46. 1 / 1
| 1

sparser
"To identify proximal proteins of USP46, we comprehensively analyzed these purified proteins of intact Neuro2a, USP46‐WT clone 6, and USP46ΔK92 clone 5 by mass spectrometry."
Vinclozolin affects USP46
1 |
Vinclozolin increases the amount of USP46. 1 / 1
1 |

No evidence text available
Topotecan affects USP46
1 |
Topotecan decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
1 |

No evidence text available
1 |
Testosterone decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Sorafenib affects USP46
1 |
Sorafenib increases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Sodium arsenite increases the amount of USP46. 1 / 1
1 |

No evidence text available
Silver(0) affects USP46
1 |
Silver(0) decreases the amount of USP46. 1 / 1
1 |

No evidence text available
SiRNA-mediated wdr48 affects USP46
| 1
SiRNA-mediated wdr48 activates USP46. 1 / 1
| 1

eidos
"Finally , siRNA-mediated knockdown of wdr48 destabilizes USP46 in mammalian cells ."
Saxitoxin affects USP46
1 |
Saxitoxin increases the amount of USP46. 1 / 1
1 |

No evidence text available
Quercetin affects USP46
1 |
Quercetin decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Potassium dichromate increases the amount of USP46. 1 / 1
1 |

No evidence text available
Polyubiquitin chains affects USP46
| 1
USP46 binds polyubiquitin chains. 1 / 1
| 1

reach
"USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP in vitro and in cells."
Piroxicam affects USP46
1 |
Piroxicam decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Pimozide affects USP46
| 1
| 1

reach
"Pimozide, flupenthixol and trifluoperazine did not inhibit USP46 and UAF1 at the highest inhibitor concentrations tested (114 muM), while low level of inhibition by GW7647 was observed (IC 50 = 12 muM, XREF_TABLE)."
Phlorizin affects USP46
1 |
Phlorizin decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Permethrin affects USP46
1 |
Permethrin demethylates USP46. 1 / 1
1 |

No evidence text available
Oxaliplatin affects USP46
1 |
Oxaliplatin decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Mono(2-ethylhexyl) phthalate decreases the amount of USP46. 1 / 1
1 |

No evidence text available
MiR-34a affects USP46
| 1
MiR-34a inhibits USP46. 1 / 1
| 1

reach
"Our study is the first to show that an anti-tumorous microRNA, miR-34a suppresses viral E6 protein (which in turn excludes USP46 from nucleus) and destabilizes overexpressed oncoprotein Cdt2 in HPV positive cell lines and stops their proliferation eventually killing these cancerous cells (Fig. 6), while no effect is seen on HPV negative cells."
Methylmercury chloride decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Methyl methanesulfonate increases the amount of USP46. 1 / 1
1 |

No evidence text available
Methimazole affects USP46
1 |
Methimazole decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Leucine affects USP46
| 1
USP46 binds PHLPP1 and leucine. 1 / 1
| 1

reach
"Recently, a proteomic study on deubiquitinating enzymes and their associated protein complexes demonstrated that USP46 interacts with PHLPP and SCOP (PH-domain leucine rich repeat protein phosphatase and suprachiasmatic nucleus circadian oscillatory protein), which are members of the of Ser/Thr family of protein phosphatases XREF_BIBR."
1 |
Hsa-mir-4457 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4303 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4294 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4282 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4280 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-3920 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6815-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6807-5p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6751-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-513c-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-513b-5p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-513a-5p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-513a-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-489-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4795-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4766-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4670-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4459 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4433b-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3688-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3681-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3606-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-338-5p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3065-5p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3064-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-27b-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-216a-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-16-2-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-128-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-125b-2-3p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-1199-5p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-106b-5p decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Hexabromocyclododecane increases the amount of USP46. 1 / 1
1 |

No evidence text available
HUAF1 affects USP46
| 1
USP46 binds hUAF1. 1 / 1
| 1

reach
"These may suggested that the activation of USP1 upon binding to UAF1 may be due to an increase in k cat with no drastic change in the K M, that was similar to what were observed on activation of human USP12 and USP46 binding to hUAF1 [XREF_BIBR] Besides hUSP1, hUAF1 stimulates hUSP12 and hUSP46 activity as well."
Folic acid affects USP46
1 |
Folic acid decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Endosulfan affects USP46
1 |
Endosulfan decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Deltamethrin increases the amount of USP46. 1 / 1
1 |

No evidence text available
Crocidolite asbestos decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Cobalt dichloride decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Circ-NNT affects USP46
| 1
Circ-NNT increases the amount of USP46. 1 / 1
| 1

reach
"Circ-NNT mediates MI/RI through activating pyroptosis by miR-33a-5p and regulating USP46 expression [64]."
Cholesterol affects USP46
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
Cas9 affects USP46
| 1
Cas9 decreases the amount of USP46. 1 / 1
| 1

reach
"Concomitant expression of Cas9 and Usp46 sgRNAs in the posterior compartment using hh-Gal4 reduced Usp46 levels in the posterior compartment, as revealed by loss of the Usp46-V5 signal (Fig. S5D, F)."
Calcitriol affects USP46
1 |
Calcitriol decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Cadmium dichloride decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Bun107 affects USP46
| 1
Bun107 activates USP46. 1 / 1
| 1

reach
"Moreover, the human ortholog of Bun107 activates USP12 and USP46 XREF_BIBR."
Bortezomib affects USP46
| 1
| 1

reach
"In particular, we found that ZOL inhibited expression of the ubiquitin-specific peptidase 24 ( USP24) a de-ubiquitin protease that is overexpressed in bortezomib-resistant RPMI-R5 cells compared to RP[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Bisphenol F affects USP46
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Bisphenol F increases the amount of USP46. 1 / 1
1 |

No evidence text available
Bis(2-ethylhexyl) phthalate decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Benzo[a]pyrene increases the amount of USP46. 1 / 1
1 |

No evidence text available
Atrazine affects USP46
1 |
Atrazine decreases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Arsenous acid increases the amount of USP46. 1 / 1
1 |

No evidence text available
1 |
Arsenic atom increases the amount of USP46. 1 / 1
1 |

No evidence text available
Antirheumatic drug increases the amount of USP46. 1 / 1
1 |

No evidence text available
Amitrole affects USP46
1 |
Amitrole decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Albumin affects USP46
| 1
USP46 binds albumin. 1 / 1
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
ZEB1 affects USP46
1 |
ZEB1 decreases the amount of USP46. 1 / 1
1 |

No evidence text available
YWHAZ affects USP46
1 |
1 |

No evidence text available
YWHAG affects USP46
1 |
1 |

No evidence text available
YWHAE affects USP46
1 |
1 |

No evidence text available
YWHAB affects USP46
1 |
1 |

No evidence text available
XPO1 affects USP46
1 |
1 |

No evidence text available
WDR77 affects USP46
1 |
1 |

No evidence text available
WDR48 affects Ubiquitin
| 1
| 1

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme ( xref and xref )."
| 1

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
WDR26 affects USP46
1 |
1 |

No evidence text available
WDR protein affects USP46
| 1
USP46 binds WDR protein. 1 / 1
| 1

reach
"We highlight recent structural insights into how WDR proteins interact with and regulate USP46, and discuss functions for the USP46 and WDR protein complex in the nervous system and across phylogeny."
WD40-repeat-containing protein affects USP46
| 1
WD40-repeat-containing protein activates USP46. 1 / 1
| 1

eidos
"USP12 and USP46 , but not USP1 , can be independently activated by another WD40-repeat-containing protein , WDR20 ( Burska et al ., 2013 ; Dahlberg and Juo , 2014 ; Kee et al ., 2010 ; McClurg et al ., 2014 ) ."
WD40-repeat protein WDR-20 affects USP46
| 1
WD40-repeat protein WDR-20 binds USP46. 1 / 1
| 1

reach
"In C. elegans and mammals, the WD40-repeat protein WDR-20 binds to WDR-48 and activates USP46."
WD40-repeat (WDR) proteins affects USP46
| 1
USP46 binds WD40-repeat (WDR) proteins. 1 / 1
| 1

reach
"Mechanistically, USP46 can bind with WD40-repeat (WDR) proteins WDR-20 and WDR-48 to stimulate USP46 catalytic activity and increase GLR-1 levels."
WD40 affects USP46
| 1
WD40 activates USP46. 1 / 1
| 1

reach
"For example, GMP synthetase (GMPS) interacts and activates USP7 (Faesen et al., 2011; Sarkari et al., 2009; van der Knaap et al., 2005), whereas the WD40 repeat containing UAF1 (WDR48) activates USP1,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
VTN affects USP46
| 1
| 1

sparser
"Consistent with the localization pattern of PLPP3-mCherry, cells co-expressing USP46-VN and PLPP3-VC showed weak but detectable fluorescence localized near the cell periphery ( xref , arrowheads), along with relatively strong signals in the cytoplasm."
VSX1 affects USP46
1 |
1 |

No evidence text available
Ubiquitin affects WDR48
| 1
| 1

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme ( xref and xref )."
USP6 affects USP46
| 1
USP6 binds USP46 and DTL. 1 / 1
| 1

sparser
"Moreover, miR-3680-5p was associated with the USP6 , USP32 , USP46 , and DTL genes, which have roles in the ubiquitin (deubiquitin) proteolysis system."
USP46-PHLPP affects USP46
| 1
USP46-PHLPP activates USP46. 1 / 1
| 1

reach
"Li et al. found that USP46 functions as a deubiquitinase to remove ubiquitin from PHLPP and stabilizes this protein, and the USP46-PHLPP mediated downregulation of AKT suggests the novel tumor suppres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects ΔK92
| 1
ΔK92 binds USP46. 1 / 1
| 1

sparser
"To identify proximal proteins of USP46, we comprehensively analyzed these purified proteins of intact Neuro2a, USP46‐WT clone 6, and USP46ΔK92 clone 5 by mass spectrometry."
USP46 affects ubiquitinated receptors
| 1
USP46 activates ubiquitinated receptors. 1 / 1
| 1

reach
"In addition, GLR-1 accumulates in the VNC of usp-46 mutants when trafficking to the MVB is blocked, suggesting that USP-46 is required to prevent the degradation of ubiquitinated receptors in the MVB and lysosome pathway."

reach
"Consequently, depletion of the Usp46 complex disrupts Wingless-directed development and tissue homeostasis."
USP46 affects tamoxifen
| 1
| 1

reach
"USP46 enhances tamoxifen resistance in breast cancer cells by stabilizing PTBP1 to facilitate glycolysis."
USP46 affects resistance ovarian cancer cisplatin
| 1
USP46 inhibits resistance ovarian cancer cisplatin. 1 / 1
| 1

eidos
"Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2 ."
USP46 affects pyroptosis
| 1
| 1

reach
"Circ-NNT and USP46 upregulated, whereas miR-33a-5p downregulated anoxia/reoxygenation (A/R)-induced cardiomyocytes pyroptosis in vitro and I/R-induced myocardial pyroptosis and infarction in vivo ."
USP46 affects proteolysis
| 1
| 1

reach
"Previous studies reported that USP46 functions as a tumor suppressor via deubiquitination of PH domain leucine-rich-repeats protein phosphatase (PHLPP) and reduces its protein degradation."

reach
"This study elucidates a novel regulatory mechanism linking USP46-mediated protein stabilization to ECM dynamics and neural cell migration, offering new insights into HSCR pathogenesis and potential therapeutic targets."
USP46 affects polyubiquitin chains
| 1
USP46 binds polyubiquitin chains. 1 / 1
| 1

reach
"USP46 binds to PHLPP and directly removes the polyubiquitin chains from PHLPP in vitro and in cells."

reach
"They revealed a novel method by which USP46 suppresses the AKT signaling pathway, hence impairing RCC survival."
| 1
| 1

reach
"USP1, USP46, and WDR20 are candidate ubiquitylation targets (XREF_FIG), as they are either only detected or APSMs increase in the presence of MLN4924 and/or Btz."
USP46 affects nodes lung metastasis ESCC
| 1
USP46 activates nodes lung metastasis ESCC. 1 / 1
| 1

eidos
"Moreover , USP46 enhances the migration and invasion of ESCC cells by mediating the EMT process in vitro , and promotes lymph nodes and lung metastasis of ESCC in vivo ."
USP46 affects migration invasion ESCC cells
| 1
USP46 activates migration invasion ESCC cells. 1 / 1
| 1

eidos
"Moreover , USP46 enhances the migration and invasion of ESCC cells by mediating the EMT process in vitro , and promotes lymph nodes and lung metastasis of ESCC in vivo ."
| 1
| 1

reach
"Our results revealed that upregulation of USP46 leads to decreased nuclear localization of YAP1, while downregulation of USP46 increased the nuclear localization of YAP1 ( Supplementary Fig. S2 B )."
USP46 affects leucine
| 1
USP46 binds PHLPP1 and leucine. 1 / 1
| 1

reach
"Recently, a proteomic study on deubiquitinating enzymes and their associated protein complexes demonstrated that USP46 interacts with PHLPP and SCOP (PH-domain leucine rich repeat protein phosphatase and suprachiasmatic nucleus circadian oscillatory protein), which are members of the of Ser/Thr family of protein phosphatases XREF_BIBR."

reach
"We therefore investigated whether Usp46 promotes this Wingless-dependent control of intestinal homeostasis."
USP46 affects hUAF1
| 1
USP46 binds hUAF1. 1 / 1
| 1

reach
"These may suggested that the activation of USP1 upon binding to UAF1 may be due to an increase in k cat with no drastic change in the K M, that was similar to what were observed on activation of human USP12 and USP46 binding to hUAF1 [XREF_BIBR] Besides hUSP1, hUAF1 stimulates hUSP12 and hUSP46 activity as well."

reach
"It is thought that Usp46 deficiency causes dysfunction of gamma-aminobutyric acid A (GABA A) receptor activity [XREF_BIBR, XREF_BIBR]."
USP46 affects endocytosis
| 1
| 1

reach
"We propose that USP-46 functions, in part, by acting prior to clathrin mediated endocytosis to prevent the degradation of newly synthesized GLR-1 delivered to an internal compartment en route to the plasma membrane."
USP46 affects cholesterol
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."

reach
"Transient depletion of USP12, USP46, and USP53 did not induce a senescence arrest."
USP46 affects cell
| 1
USP46 inhibits cell. 1 / 1
| 1

eidos
"Furthermore , we found that USP46 suppresses HCC cell proliferation and metastasis by inhibiting YAP1 ."
| 1

reach
"In LC cells growing normally and in cells exposed to IR, USP46 effectively prevents cell division."
USP46 affects cell apoptosis
| 1
USP46 activates cell apoptosis. 1 / 1
| 1

eidos
"In SKOV3 / DDP cells , the upregulation of USP46 expression levels notably suppressed cell viability and increased cell apoptosis ."
USP46 affects albumin
| 1
USP46 binds albumin. 1 / 1
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
USP46 affects ZNRF3
| 1
USP46 decreases the amount of ZNRF3. 1 / 1
| 1

reach
"Expression of the RNF43 homolog, ZNRF3, similarly increased ubiquitylation of LRP6-FLAG in LF203 cells and was also blocked by expression of the USP46 complex (Supplementary Fig. 6D)."
USP46 affects ZNFR3
| 1
USP46 inhibits ZNFR3. 1 / 1
| 1

reach
"In contrast, overexpression of the USP46 complex blocks ubiquitylation of LRP6 by the ubiquitin ligases RNF43 and ZNFR3."
USP46 affects YWHAZ
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1 |

No evidence text available
USP46 affects YWHAG
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1 |

No evidence text available
USP46 affects YWHAE
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1 |

No evidence text available
USP46 affects YWHAB
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1 |

No evidence text available
USP46 affects XPO1
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1 |

No evidence text available
USP46 affects Wnt co-receptor
| 1
USP46 leads to the deubiquitination of Wnt co-receptor. 1 / 1
| 1

reach
"The USP46 complex blocks ubiquitylation/degradation of the Wnt co-receptor LRP6 [33]."
USP46 affects Wingless target gene
| 1
USP46 inhibits Wingless target gene. 1 / 1
| 1

reach
"Usp46 inactivation in Wingless-responding cells destabilizes Arrow, reduces cytoplasmic accumulation of the transcriptional coactivator Armadillo/beta-catenin, and attenuates or abolishes Wingless target gene activation, which prevents the concentration-dependent regulation of signaling strength."
USP46 affects WDR77
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1 |

No evidence text available
USP46 affects WDR26
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1 |

No evidence text available
USP46 affects WDR protein
| 1
USP46 binds WDR protein. 1 / 1
| 1

reach
"We highlight recent structural insights into how WDR proteins interact with and regulate USP46, and discuss functions for the USP46 and WDR protein complex in the nervous system and across phylogeny."
USP46 affects WD40-repeat protein WDR-20
| 1
WD40-repeat protein WDR-20 binds USP46. 1 / 1
| 1

reach
"In C. elegans and mammals, the WD40-repeat protein WDR-20 binds to WDR-48 and activates USP46."
USP46 affects WD40-repeat (WDR) proteins
| 1
USP46 binds WD40-repeat (WDR) proteins. 1 / 1
| 1

reach
"Mechanistically, USP46 can bind with WD40-repeat (WDR) proteins WDR-20 and WDR-48 to stimulate USP46 catalytic activity and increase GLR-1 levels."
USP46 affects VTN
| 1
| 1

sparser
"Consistent with the localization pattern of PLPP3-mCherry, cells co-expressing USP46-VN and PLPP3-VC showed weak but detectable fluorescence localized near the cell periphery ( xref , arrowheads), along with relatively strong signals in the cytoplasm."
USP46 affects VSX1
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1 |

No evidence text available
USP46 affects Ubiquitin, and WDR48
| 1
| 1

sparser
"Reminiscent of the Ub-bound UAF1-USP46 complex, the UAF1-USP12 structure features an L-shaped architecture, in which the elongated UAF1 protein packs perpendicularly against the DUB enzyme ( xref and xref )."
USP46 affects USP6
| 1
USP6 binds USP46 and DTL. 1 / 1
| 1

sparser
"Moreover, miR-3680-5p was associated with the USP6 , USP32 , USP46 , and DTL genes, which have roles in the ubiquitin (deubiquitin) proteolysis system."
USP46 affects USH1C
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1 |

No evidence text available
USP46 affects UBE3A
| 1
E6 binds UBE3A, TP53, and USP46. 1 / 1
| 1

sparser
"E6 associates specifically with USP46+Cdt2 independent of E6AP, p53 and USP46 accessory proteins."
USP46 affects UBC
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1 |

No evidence text available
USP46 affects UBB
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1 |

No evidence text available
USP46 affects UBA52
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1 |

No evidence text available
USP46 affects TST
| 1
USP46 inhibits TST. 1 / 1
| 1

reach
"Importantly, the decreased TST and FST immobility and the defects in the GABA system observed in CS mice could be rescued by expression of Usp46 from a BAC transgene [XREF_BIBR]."
USP46 affects TP53
| 1
E6 binds UBE3A, TP53, and USP46. 1 / 1
| 1

sparser
"E6 associates specifically with USP46+Cdt2 independent of E6AP, p53 and USP46 accessory proteins."
USP46 affects TIMM8A
| 1
USP46 activates TIMM8A. 1 / 1
| 1

reach
"Similarly, in SKOV3 and DDP cells, the overexpression of PUM2 could reverse DDP sensitivity induced by the overexpression of USP46."
USP46 affects Ser351
| 1
CK1delta binds USP46 and Ser351. 1 / 1
| 1

reach
"CK1delta binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."
USP46 affects Seizures
| 1
| 1

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"Variants of the USP46 gene affect neurotransmitter systems, contributing to mood disorders, cognitive impairments, and increased seizure susceptibility."
USP46 affects SP1
| 1
USP46 inhibits SP1. 1 / 1
| 1

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"SP1 could enhance the transcription of USP46, and USP46 overexpression reversed SP1 silencing-mediated effects on OGD/R-induced cardiomyocytes."
USP46 affects SHOC2
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1 |

No evidence text available
USP46 affects SGO1
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1 |

No evidence text available
USP46 affects SET
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1 |

No evidence text available

reach
"Circ-NNT and USP46 upregulated, whereas miR-33a-5p downregulated anoxia/reoxygenation (A/R)-induced cardiomyocytes pyroptosis in vitro and I/R-induced myocardial pyroptosis and infarction in vivo ."
USP46 affects RSPO
| 1
USP46 inhibits RSPO. 1 / 1
| 1

reach
"Because the USP46 complex opposes the action of RNF43 and ZNRF3, loss of USP46 would be expected to potentiate the activities of RNF43 and ZNRF3, decreasing the effectiveness of RSPO in maintaining intestinal organoid growth."
USP46 affects RPS6KB1
| 1
USP46 leads to the dephosphorylation of RPS6KB1. 1 / 1
| 1

reach
"On the contrary, the depletion of USP46 markedly promoted AKT phosphorylation and S6K1 phosphorylation ( Fig. 4 B)."
USP46 affects RAP1GDS1
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
USP46 affects PPP1R9B
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No evidence text available
USP46 affects POU4F1
| 1
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sparser
"Through IP-MS, GST pull-down, and co-immunoprecipitation assays, it is demonstrated that USP46 interacts with the transcription factor POU4F1."
USP46 affects PON2
| 1

sparser
"In this study, we explored the association between ncRNA expression and glioma OS, and obtained a prognostic signature containing three ncRNAs, including USP46AS1 , PON2 and LOC441179 , based on which we could accurately separate glioma patients with better prognosis from those with a worse prognosis."
USP46 affects PJA2
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1 |

No evidence text available
USP46 affects PEMT
| 1
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
USP46 affects PARP1
| 1
USP46 inhibits PARP1. 1 / 1
| 1

reach
"Furthermore, reduced expression of USP46 contributes to cisplatin resistance by suppressing the apoptotic mediators Caspase3, Bax, and poly‑ADP ribose polymerase (PARP), while concurrently activating BCL2."
USP46 affects OPALIN
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1 |

No evidence text available
USP46 affects NFS1
| 1
USP46 inhibits NFS1. 1 / 1
| 1

reach
"These findings reveal that in a manner similar to known Wingless pathway components, the Usp46 complex non-autonomously restricts proliferation of neighboring ISCs, providing additional evidence that Usp46 promotes Wingless signaling during intestinal homeostasis."
USP46 affects Mice
| 1
USP46 activates Mice. 1 / 1
| 1

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"We observed that knockdown of USP46 led to decreased HIF-1α levels and reduction in glycolysis rate, thereby attenuating myocardial hypertrophy in mice model of cardiac hypertrophy."
USP46 affects MYL6
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1 |

No evidence text available
USP46 affects MYC
| 1
| 1

sparser
"Myc-WDR20, Myc-USP12, Myc-USP12 delMEIL and Myc-USP46 were generated by cloning WDR20, USP12, USP12 delMEIL and USP46 cDNAs into pMyc-MCS, a modified version of pEYFP-C1 where the Myc epitope replaces[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects MVD1
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sparser
"Firstly, the association of USP46 gene with MDD patients may be due to biased samples, such as small sample sizes or unmatched age."
USP46 affects MTOR
| 1
USP46 leads to the phosphorylation of MTOR. 1 / 1
| 1

reach
"In the present study, it was revealed that downregulation of USP46 expression levels could also promote the phosphorylation of AKT and mTOR, while the overexpression of USP46 could inhibit the phosphorylation levels."
| 1

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
USP46 affects MST1
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USP46 deubiquitinates MST1. 1 / 1
1 |

"Moreover, <span class="match term0">USP46</span> acts as a deubiquitinating enzyme of <span class="match term1">MST1</span> to potentiate <span class="match term1">MST1</span> kinase activity to suppress tumor growth and metastasis, indicating that <span class="match term0">USP46</span> activation may represent a potential treatment strategy for HCC."
USP46 affects MKI67
| 1
USP46 increases the amount of MKI67. 1 / 1
| 1

reach
"We also found that the depletion of USP46 in SK-MEL-103 cells dramatically reduced Ki67 expression along with upregulated cleaved caspase-3 staining in tumors from mice treated with saline or DTIC, although the phenotypical alterations were much more obvious in DTIC-treated group."
USP46 affects MIR mice
| 1
USP46 activates MIR mice. 1 / 1
| 1

reach
"miR-33–5p was found to be downregulated in MIR injury patients and mice, and anoxia/reoxygenation (A/R)-stimulated cardiomyocytes directly downregulate ubiquitin-specific peptidase 46 (USP46) gene exp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects METTL3
| 1
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sparser
"In addition, we also demonstrated that p300 could bind to METTL3 promoter in NRCMs, while USP46 did not bind to METTL3 promoter ( Supplementary Fig. 4F )."
USP46 affects MAVS
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No evidence text available
USP46 affects MAPK8IP2
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No evidence text available
USP46 affects M
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M binds USP46. 1 / 1
1 |

No evidence text available
| DOI
USP46 affects LRP6 receptors
| 1
USP46 binds LRP6 receptors. 1 / 1
| 1

reach
"Based on these findings, we conclude that the USP46 complex associates with activated LRP6 receptors but not LRP6 signalosome aggregates."
USP46 affects LATS1
| 1
| 1

sparser
"However, our immunoprecipitation results showed no interaction between USP46 and LATS1 ( Supplementary Fig. S2 F )."
USP46 affects K63
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sparser
"These functions of CYLD were implied in a study on another K63-DUB, USP46, which can cleave K63-linked ubiquitination chains from AMPARs and modulate AMPAR internalization and turnover in cultured rat cortical and hippocampal neurons; in this way, USP46 is thought to regulate AMPAR-mediated excitatory synaptic transmission ( xref )."
USP46 affects Infarction
| 1
| 1

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"Circ-NNT and USP46 upregulated, whereas miR-33a-5p downregulated anoxia/reoxygenation (A/R)-induced cardiomyocytes pyroptosis in vitro and I/R-induced myocardial pyroptosis and infarction in vivo ."
USP46 affects ITGB1
| 1
Mutated USP46 increases the amount of ITGB1. 1 / 1
| 1

reach
"In contrast, re-expression of the catalytically inactive USP12 or USP46 mutants, in which the catalytic site cysteine was substituted for serine (Li et al, 2016; Yin et al, 2015), were unable to restore the Itgb1 levels indicating that USP12/46 require the DUB activity to maintain the 125 kDa mature Itgb1 levels (Figs."
USP46 affects ISC
| 1
USP46 inhibits ISC. 1 / 1
| 1

reach
"We conclude that the Usp46 complex restricts ISC proliferation but is dispensable for asymmetric stem cell division, properties shared with known positive regulators in the Wingless signaling pathway.In the adult posterior midgut, the ability of enterocytes to non-autonomously restrict the proliferation of neighboring ISCs requires Wingless signaling ."
USP46 affects IGDCC4
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1 |

No evidence text available
USP46 affects Hypertrophy
| 1
| 1

reach
"We observed that knockdown of USP46 led to decreased HIF-1α levels and reduction in glycolysis rate, thereby attenuating myocardial hypertrophy in mice model of cardiac hypertrophy."
USP46 affects HIF1
| 1
USP46 activates HIF1. 1 / 1
| 1

reach
"We observed that knockdown of USP46 led to decreased HIF-1α levels and reduction in glycolysis rate, thereby attenuating myocardial hypertrophy in mice model of cardiac hypertrophy."
USP46 affects H2BC9
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1 |

No evidence text available
USP46 affects GPR15
| 1
GPR15 binds USP46, CCR4, and CCR8. 1 / 1
| 1

sparser
"GPR15, RTKN2 , USP46, CCR4, and CCR8 formed a cluster of genes up-regulated in smokers ( Figure 3 )."
USP46 affects GAD1
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USP46 deubiquitinates GAD1. 1 / 1
1 |

No evidence text available
USP46 affects FlaG
| 1
| 1

sparser
"Interestingly, we also identified CK1δ as a major USP46-associated protein by tandem affinity purification and mass spectrometry analysis using SK-MEL-103 cells stably expressing FLAG-USP46 (Fig. xref )."
USP46 affects Fibrinogen
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
USP46 affects ESCC
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USP46 activates ESCC. 1 / 1
| 1

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"Our studies illustrated that USP46 could strikingly promote cell migration, invasion and tumor metastasis of ESCC."
USP46 affects ERP44
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1 |

No evidence text available
USP46 affects EPHA2
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1 |

No evidence text available
USP46 affects EIF2AK4
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1 |

No evidence text available
USP46 affects EBNA6
| 1
| 1

reach
"EBNA3C interactions with RBPJ, CtBP, WDR48, and USP46 are also important for EBNA3C-mediated p16 repression [92,93,111] (Figure 1)."
USP46 affects Casp4
| 1
USP46 decreases the amount of Casp4. 1 / 1
| 1

reach
"miR-33–5p-mediated downregulation of USP46 expression inhibits the expression of caspase-11 and activation of caspase-11 non-canonical inflammasomes in A/R-stimulated cardiomyocytes [75] , suggesting [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Collectively, our results indicated that miR-27a targets USP46 to promote EC cell proliferation and migration, suggesting an oncogene role of miR-27a in EC."
| 1

reach
"We next investigate whether USP46 promotes tumorigenesis and progression of melanoma harboring NRAS Q61R/K mutants."
USP46 affects CSNK1
| 1
| 1

reach
"Second, CK1δ binds and regulates the phosphorylation of USP46 (Fig. 6 and Supplementary Fig. 9)."
USP46 affects CK1delta
| 1
CK1delta binds USP46 and Ser351. 1 / 1
| 1

reach
"CK1delta binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."
USP46 affects CCR8
| 1
GPR15 binds USP46, CCR4, and CCR8. 1 / 1
| 1

sparser
"GPR15, RTKN2 , USP46, CCR4, and CCR8 formed a cluster of genes up-regulated in smokers ( Figure 3 )."
USP46 affects CASC3
| 1
USP46 activates CASC3. 1 / 1
| 1

reach
"USP1, USP46, and WDR20 are candidate ubiquitylation targets (XREF_FIG), as they are either only detected or APSMs increase in the presence of MLN4924 and/or Btz."
USP46 affects BECN1
| 1
| 1

sparser
"USP46's interaction with beclin 1 (BECN1) was evaluated using immunoprecipitation assays, whereas BECN1 knockdown was performed with siRNA."
USP46 affects Arm/β-catenin
| 1
USP46 activates Arm/β-catenin. 1 / 1
| 1

reach
"These findings provide in vivo evidence that the Usp46 complex increases signaling strength by stabilizing Arrow/LRP6 and consequently promoting the cytoplasmic accumulation of Arm/β-catenin in Wingless-responding cells."
USP46 affects ATG9A
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1 |

No evidence text available
USP46 affects AS
| 1
| 1

sparser
"Lei et al. identified a five angiogenesis-related lncRNA signature (LINC01138, LINC00942, AL031985.3, AC015908.3 and USP46-AS) as an independent prognostic biomarker for predicting hepatocellular carcinoma patient survival [ xref ]."
USP46 affects AMPA receptors
| 1
USP46 deubiquitinates AMPA receptors. 1 / 1
| 1

reach
"Given the same type of deubiquitinating enzyme (USP46) is able to deubiquitinate AMPA receptors, and knockdown of USP46 elevated AMPA receptor ubiquitination and reduced AMPA receptor expression in hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP46 affects ALDH9A1
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1 |

No evidence text available

reach
"In contrast to hypoxic conditions, targeting of Usp46 increased MTT viability under normoxic conditions."
USP46 affects 293T
| 1
USP46 binds PHLPP1 and 293T. 1 / 1
| 1

reach
"Co-immunoprecipitation experiments showed that only USP46 specifically interacted with PHLPP1 in transfected 293T cells whereas other DUBs including USP7 and USP16 failed to binding PHLPP1, thus, demonstrating the specificity of USP46 mediated interaction (XREF_FIG)."
USP12 affects USP46, WDR20, and WDR48
| 1
| 1

sparser
"WDR20 forms a unique ternary complex with WDR48 and either USP12 or USP46 (Sowa et al., xref ; Kee et al., xref ) and further enhances their catalytic activity in vitro (Kee et al., xref ; Faesen et al., xref )."
USP12 affects TBK1
| 1
USP12 binds USP46 and TBK1. 1 / 1
| 1

sparser
"In addition, USP12 and USP46 were not associated with TBK1 ( xref )."
| 1

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
USP12 affects DMWD
| 1
DMWD binds USP12 and USP46. 1 / 1
| 1

sparser
"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
USH1C affects USP46
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1 |

No evidence text available
UBE3A affects USP46
| 1
E6 binds UBE3A, TP53, and USP46. 1 / 1
| 1

sparser
"E6 associates specifically with USP46+Cdt2 independent of E6AP, p53 and USP46 accessory proteins."
UBC affects USP46
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1 |

No evidence text available
UBB affects USP46
1 |
1 |

No evidence text available
UBA52 affects USP46
1 |
1 |

No evidence text available
UAF1 elusive affects USP46
| 1
UAF1 elusive activates USP46. 1 / 1
| 1

eidos
"However , a structural comparison of the enzyme in these two post-reaction forms revealed few conformational differences , leaving the mechanism of USP46 activation by UAF1 elusive ."
TP53 affects USP46
| 1
E6 binds UBE3A, TP53, and USP46. 1 / 1
| 1

sparser
"E6 associates specifically with USP46+Cdt2 independent of E6AP, p53 and USP46 accessory proteins."
TGM1 affects USP46
| 1
TGM1 decreases the amount of USP46. 1 / 1
| 1

reach
"https://doi.org/10.3892/mmr.2021.12024.The images for Figure 4A, sh-LINC01260 and sh-Control have been duplicated with the images for Figure 3A, NC and miR-613 mimics, respectively, from Luo et al, 2021.Images for Figure 4F have been duplicated with images for Figure 1D from Xu L, Zhang B, Li W. Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2."
TBK1 affects USP46
| 1
USP12 binds USP46 and TBK1. 1 / 1
| 1

sparser
"In addition, USP12 and USP46 were not associated with TBK1 ( xref )."
Ser351 affects USP46
| 1
CK1delta binds USP46 and Ser351. 1 / 1
| 1

reach
"CK1delta binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."
SP1 affects USP46
| 1
SP1 increases the amount of USP46. 1 / 1
| 1

reach
"SP1 could enhance the transcription of USP46, and USP46 overexpression reversed SP1 silencing-mediated effects on OGD/R-induced cardiomyocytes."
SHOC2 affects USP46
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1 |

No evidence text available
SGO1 affects USP46
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1 |

No evidence text available
SET affects USP46
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1 |

No evidence text available
Rimonabant affects USP46
1 |
Rimonabant decreases the amount of USP46. 1 / 1
1 |

No evidence text available
Reperfusion Injury increases the amount of USP46. 1 / 1
| 1

reach
"USP46 expression is stimulated by I/R, and its overexpression enhances ferroptosis in I/R-treated neuronal cells."
RNAi affects USP46
| 1
RNAi inhibits USP46. 1 / 1
| 1

reach
"By contrast, knockdown of USP46 by RNAi leads to elevated AMPAR ubiquitination and a reduction in surface AMPARs at synapses in neurons."
RAP1GDS1 affects USP46
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
PPP1R9B affects USP46
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1 |

No evidence text available
POU4F1 affects USP46
| 1
| 1

sparser
"Through IP-MS, GST pull-down, and co-immunoprecipitation assays, it is demonstrated that USP46 interacts with the transcription factor POU4F1."
PON2 affects USP46
| 1

sparser
"In this study, we explored the association between ncRNA expression and glioma OS, and obtained a prognostic signature containing three ncRNAs, including USP46AS1 , PON2 and LOC441179 , based on which we could accurately separate glioma patients with better prognosis from those with a worse prognosis."
PJA2 affects USP46
1 |
1 |

No evidence text available
PHLPP1 affects leucine
| 1
USP46 binds PHLPP1 and leucine. 1 / 1
| 1

reach
"Recently, a proteomic study on deubiquitinating enzymes and their associated protein complexes demonstrated that USP46 interacts with PHLPP and SCOP (PH-domain leucine rich repeat protein phosphatase and suprachiasmatic nucleus circadian oscillatory protein), which are members of the of Ser/Thr family of protein phosphatases XREF_BIBR."
PHLPP1 affects 293T
| 1
USP46 binds PHLPP1 and 293T. 1 / 1
| 1

reach
"Co-immunoprecipitation experiments showed that only USP46 specifically interacted with PHLPP1 in transfected 293T cells whereas other DUBs including USP7 and USP16 failed to binding PHLPP1, thus, demonstrating the specificity of USP46 mediated interaction (XREF_FIG)."
PEMT affects USP46
| 1
| 1

reach
"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
OPALIN affects USP46
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1 |

No evidence text available
NEDD4 affects USP46
| 1
NEDD4 decreases the amount of USP46. 1 / 1
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"These include : (a) overexpression of Nedd4-1 in neurons, which enhances GluA1 ubiquitination, causes a reduction in the number of AMPARs on the plasma membrane; (b) shRNA mediated knockdown of Nedd4-1 increases the rate of GluA1 internalization; (c) overexpression of USP46, which downregulates GluA1 ubiquitination, decreases the accumulation of internalized GluA1 in neurons; and (d) overexpression of GluA1-4KR ubiquitin deficient mutants (where all four C-terminal lysine residues have been substituted with arginines) blocks AMPA induced GluA1 internalization."

No evidence text available
MYL6 affects USP46
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MYC affects USP46
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sparser
"Myc-WDR20, Myc-USP12, Myc-USP12 delMEIL and Myc-USP46 were generated by cloning WDR20, USP12, USP12 delMEIL and USP46 cDNAs into pMyc-MCS, a modified version of pEYFP-C1 where the Myc epitope replaces[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
MVD1 affects USP46
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sparser
"Firstly, the association of USP46 gene with MDD patients may be due to biased samples, such as small sample sizes or unmatched age."
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sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
MIR375 affects USP46
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MIR375 decreases the amount of USP46. 1 / 1
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MIR1179 affects USP46
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MIR1179 decreases the amount of USP46. 1 / 1
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MIR106B affects USP46
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MIR106B decreases the amount of USP46. 1 / 1
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"Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. (See supplemental Table 1: Supplementary Table 1. miR-106b family signature. A consensus set of genes that were significantly down-regulated by miR-106a, miR-106b, miR-17-5p, and miR-20)"
MIR106A affects USP46
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MIR106A decreases the amount of USP46. 1 / 1
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"Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. (See supplemental Table 1: Supplementary Table 1. miR-106b family signature. A consensus set of genes that were significantly down-regulated by miR-106a, miR-106b, miR-17-5p, and miR-20)"
METTL3 affects USP46
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sparser
"In addition, we also demonstrated that p300 could bind to METTL3 promoter in NRCMs, while USP46 did not bind to METTL3 promoter ( Supplementary Fig. 4F )."
MAVS affects USP46
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MAPK8IP2 affects USP46
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No evidence text available
M affects USP46
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M binds USP46. 1 / 1
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No evidence text available
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LRP6 receptors affects USP46
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USP46 binds LRP6 receptors. 1 / 1
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"Based on these findings, we conclude that the USP46 complex associates with activated LRP6 receptors but not LRP6 signalosome aggregates."
LATS1 affects USP46
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sparser
"However, our immunoprecipitation results showed no interaction between USP46 and LATS1 ( Supplementary Fig. S2 F )."
K63 affects USP46
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sparser
"These functions of CYLD were implied in a study on another K63-DUB, USP46, which can cleave K63-linked ubiquitination chains from AMPARs and modulate AMPAR internalization and turnover in cultured rat cortical and hippocampal neurons; in this way, USP46 is thought to regulate AMPAR-mediated excitatory synaptic transmission ( xref )."
IL17RB affects DTL
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USP46 binds DTL and IL17RB. 1 / 1
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sparser
"Immunoprecipitates of myc-USP46 contained Cdt2 and DDB1 indicating that USP46 associates with CRL4-Cdt2 complex ( xref )."
IGDCC4 affects USP46
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No evidence text available
H2BC9 affects USP46
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No evidence text available
H2BC21 affects USP46
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H2AC20 affects USP46
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GSK-J4 affects USP46
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GSK-J4 increases the amount of USP46. 1 / 1
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No evidence text available
GRIA1 affects USP46
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GPR15 affects USP46
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GPR15 binds USP46, CCR4, and CCR8. 1 / 1
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sparser
"GPR15, RTKN2 , USP46, CCR4, and CCR8 formed a cluster of genes up-regulated in smokers ( Figure 3 )."
FlaG affects USP46
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sparser
"Interestingly, we also identified CK1δ as a major USP46-associated protein by tandem affinity purification and mass spectrometry analysis using SK-MEL-103 cells stably expressing FLAG-USP46 (Fig. xref )."
Fibrinogen affects USP46
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"The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen."
ERP44 affects USP46
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No evidence text available
EPHA2 affects USP46
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No evidence text available
EIF2AK4 affects USP46
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No evidence text available
EBNA3 proteins affects USP46
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EBNA3 proteins activates USP46. 1 / 1
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"We speculated that the EBNA3 proteins may target the USP46 complex primarily via interactions with WDR48 and that, in our overexpression assay, only a small portion of the WDR20 or USP46 was complexed by endogenous WDR48."
E6 affects UBE3A
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E6 binds UBE3A, TP53, and USP46. 1 / 1
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"E6 associates specifically with USP46+Cdt2 independent of E6AP, p53 and USP46 accessory proteins."
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Dietary Fats increases the amount of USP46. 1 / 1
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No evidence text available
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sparser
"In this study, we explored the association between ncRNA expression and glioma OS, and obtained a prognostic signature containing three ncRNAs, including USP46AS1 , PON2 and LOC441179 , based on which we could accurately separate glioma patients with better prognosis from those with a worse prognosis."
DTL affects USP6
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USP6 binds USP46 and DTL. 1 / 1
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"Moreover, miR-3680-5p was associated with the USP6 , USP32 , USP46 , and DTL genes, which have roles in the ubiquitin (deubiquitin) proteolysis system."
DTL affects IL17RB, and USP46
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USP46 binds DTL and IL17RB. 1 / 1
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"Immunoprecipitates of myc-USP46 contained Cdt2 and DDB1 indicating that USP46 associates with CRL4-Cdt2 complex ( xref )."
DMWD affects USP12, and USP46
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DMWD binds USP12 and USP46. 1 / 1
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"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
Cuprizon affects USP46
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Cuprizon decreases the amount of USP46. 1 / 1
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No evidence text available
Circ-NNT affects USP46
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Circ-NNT activates USP46. 1 / 1
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"Circ-NNT promotes pyroptosis and myocardial I/R injury by acting as a miR-33a-5p sponge to regulate USP46."
Caenorhabditis elegans homologs WDR20 WDR48 known UAF1 affects USP46
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Caenorhabditis elegans homologs WDR20 WDR48 known UAF1 activates USP46. 1 / 1
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eidos
"Interestingly , the Caenorhabditis elegans homologs of WDR20 and WDR48 ( also known as UAF1 ) can bind to and activate USP46 ."
CPVL affects FKBP5, FOSL2, GADD45B, PTGS1, USP46, and ZNF423
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"Some hub genes with high interactions such as USP46, CPVL, FKBP5, FOSL2, GADD45B, PTGS1, and ZNF423 were identified in the PPI and TFs network."
CK1delta affects USP46
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CK1delta binds USP46 and Ser351. 1 / 1
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"CK1delta binds and phosphorylates USP46 at Thr209, Ser351 and Ser354."
CCR8 affects USP46
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GPR15 binds USP46, CCR4, and CCR8. 1 / 1
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sparser
"GPR15, RTKN2 , USP46, CCR4, and CCR8 formed a cluster of genes up-regulated in smokers ( Figure 3 )."
CAT affects USP46
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CAT activates USP46. 1 / 1
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"Given the distinct binding mode elucidated here, it is less straightforward to reconcile this structure with direct active-site modulation, yet we propose a mechanism centered on WDR48 dependent USP s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
BECN1 affects USP46
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"USP46's interaction with beclin 1 (BECN1) was evaluated using immunoprecipitation assays, whereas BECN1 knockdown was performed with siRNA."
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Alzheimer Disease decreases the amount of USP46. 1 / 1
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"Furthermore, AD brain lysates and Abeta incubated neurons show increased expression of the AMPAR E3 ligase Nedd4 and decreased expression of AMPAR deubiquitinase USP46."
Acrylamide affects USP46
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Acrylamide decreases the amount of USP46. 1 / 1
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ATG9A affects USP46
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AS affects USP46
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"Lei et al. identified a five angiogenesis-related lncRNA signature (LINC01138, LINC00942, AL031985.3, AC015908.3 and USP46-AS) as an independent prognostic biomarker for predicting hepatocellular carcinoma patient survival [ xref ]."
APP affects USP46
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APP decreases the amount of USP46. 1 / 1
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"Furthermore, AD brain lysates and Abeta incubated neurons show increased expression of the AMPAR E3 ligase Nedd4 and decreased expression of AMPAR deubiquitinase USP46."
AMPK affects USP46
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AMPK increases the amount of USP46. 1 / 1
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"SP1 mediated OGD/R-induced cardiomyocyte inflammation, OxS injury, apoptosis, and ferroptosis by inactivating the AMPK signaling via enhancing the transcription of USP46."
ALDH9A1 affects USP46
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No evidence text available
4-hydroxyphenyl retinamide decreases the amount of USP46. 1 / 1
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No evidence text available

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293T affects USP46
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USP46 binds PHLPP1 and 293T. 1 / 1
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"Co-immunoprecipitation experiments showed that only USP46 specifically interacted with PHLPP1 in transfected 293T cells whereas other DUBs including USP7 and USP16 failed to binding PHLPP1, thus, demonstrating the specificity of USP46 mediated interaction (XREF_FIG)."
2,6-dinitrotoluene increases the amount of USP46. 1 / 1
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No evidence text available

No evidence text available