IndraLab

Statements


WDR48 affects USP12
18 | 107 50
WDR48 binds USP12.
18 | 75 31
18 | 52 14

reach
"Furthermore, forced USP12 expression significantly potentiated the protein stability of PPM1B (Supplementary Fig. 3d), and the knockdown of WDR48, a binding partner of USP12 that was reported to contribute to USP12 deubiquitinase activity , suppressed PPM1B expression (Supplementary Fig. 3e)."

No evidence text available

reach
"XREF_BIBR Notably, a recent study that screened a panel with 22 deubiquitinating enzymes in vitro showed that galeterone inhibits the enzymatic activity of USP12 and also binds directly to the USP12 and USP12 and UAF1 complexes, which dephosphorylate AKT."

reach
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."

reach
"Interestingly, the addition of WDR20 to the USP12 and UAF1 complex further increased USP12 's DUB activity."

No evidence text available

reach
"Here, we report the crystal structure of the USP12-Ub and UAF1 complex at a resolution of 2.8 A and of UAF1 at 2.3 A."

reach
"In this regard, it has been reported that, besides USP1, UAF1 also binds and regulates the activity of two other DUBs, namely USP12 and USP46 XREF_BIBR."

reach
"USP1-associated factor 1 (UAF1), which is also called WD repeat-containing protein 48, can bind USP1, USP12, and USP46 and stimulate the activity of these ubiquitin-specific proteases (USPs) (6)."

reach
"The UAF1/USP12 complex deubiquitinates PHLPP1 and suppresses the proliferation of tumor cells (41)."
| 20 2

reach
"Firstly, we confirm the presence of the Usp12, Uaf-1, and WDR20 complex in PC cells and demonstrate the importance of Uaf-1 and WDR20 for Usp12 stabilisation."

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."

reach
"Overall, the UAF1, USP12, and WDR20 complex is distinguished from the two free USP12 structures and the two UAF1 and USP12 complex structures by the apparent stabilization of most flexible structural elements found in the DUB enzyme."

reach
"Overall these results highlight the potential importance of the Usp12, Uaf-1, and WDR20 complex in AR regulation and PC progression."

reach
"Highlights : Androgen receptor is a key transcriptional regulator in prostate cancer Usp12, Uaf-1, and WDR20 complex plays a crucial role in androgen receptor stability and activity Destabilising an individual Usp12, Uaf-1, and WDR20 complex member reduces the protein levels of the whole complex and diminishes androgen receptor activity Protein levels of all members of the Usp12, Uaf-1, and WDR20 complex are significantly increased in PC INTRODUCTION."

reach
"During revision of this manuscript, a structure for the USP12, UAF1, and WDR20 complex was published."

sparser
"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center."

reach
"For example, silencing of USP12 cofactors, Usp1-associated factor 1 (UAF1), or WD repeat domain 20 (WDR20), could influence the UAF1/WDR20/USP12 complex, thus inhibiting USP12 activity and AR-mediated transcription, leading to attenuated colony formation and promoting apoptosis [105]."

reach
"The USP46-WDR48-WDR20 and the USP12-WDR48-WDR20 complex have a very comparable overall structure."

reach
"Olazabal-Herrero et al (88) revealed that WDR20 facilitates shuttling of the USP12/UAF1/WDR20 complex between the plasma membrane, cytoplasm and nucleus via the CRM1 pathway, which requires the N-terminal motif of USP12 and the novel NES of WDR20.7."
| 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 ]."
| 2

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pY701-STAT1."

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pSTAT1."

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 binds USP12 and F219. 1 / 1
| 1

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
| 1

sparser
"We confirmed the association of endogenous PHLPP1 with WDR48 and USP12 by immunoprecipitation with PHLPP1 antibody ( xref B )."
WDR48 activates USP12.
| 30 19
WDR48 activates USP12. 10 / 49
| 29 19

sparser
"UAF1 activates USP12 by binding to the tip of its Fingers domain and transmitting a long-range allosteric signal to BL1."

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

reach
"Ning Zheng (USA) presented molecular studies of USP12, revealing that UAF1 and WDR20 potentiate USP12 catalytic activity."

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)."

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]."

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

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

reach
"To delineate the mechanism by which UAF1 activates USP12, we next determined the crystal structure of USP12 in complex with full-length human UAF1 in F222 space group at 3.2 A (XREF_SUPPLEMENTARY)."
WDR48 activates USP12-E190K. 1 / 1
| 1

reach
"Wild type UAF1 was unable to activate USP12 E190K to similar levels as compared to USP12 WT (XREF_FIG d, e) and similarly, the UAF1 3X mutant did no longer activate."
WDR48 decreases the amount of USP12.
| 1
WDR48 decreases the amount of USP12. 1 / 3
| 1

reach
"As Uaf-1 and WDR20 depletion reduces Usp12 levels their silencing has a comparable effect on the AR as the Usp12 depletion alone."
WDR48 deubiquitinates USP12.
| 1
WDR48 deubiquitinates USP12. 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."
USP12 affects WDR48
18 | 80 32
USP12 binds WDR48.
18 | 75 31
18 | 52 14

reach
"Furthermore, forced USP12 expression significantly potentiated the protein stability of PPM1B (Supplementary Fig. 3d), and the knockdown of WDR48, a binding partner of USP12 that was reported to contribute to USP12 deubiquitinase activity , suppressed PPM1B expression (Supplementary Fig. 3e)."

No evidence text available

reach
"XREF_BIBR Notably, a recent study that screened a panel with 22 deubiquitinating enzymes in vitro showed that galeterone inhibits the enzymatic activity of USP12 and also binds directly to the USP12 and USP12 and UAF1 complexes, which dephosphorylate AKT."

reach
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."

reach
"Interestingly, the addition of WDR20 to the USP12 and UAF1 complex further increased USP12 's DUB activity."

No evidence text available

reach
"Here, we report the crystal structure of the USP12-Ub and UAF1 complex at a resolution of 2.8 A and of UAF1 at 2.3 A."

reach
"In this regard, it has been reported that, besides USP1, UAF1 also binds and regulates the activity of two other DUBs, namely USP12 and USP46 XREF_BIBR."

reach
"USP1-associated factor 1 (UAF1), which is also called WD repeat-containing protein 48, can bind USP1, USP12, and USP46 and stimulate the activity of these ubiquitin-specific proteases (USPs) (6)."

reach
"The UAF1/USP12 complex deubiquitinates PHLPP1 and suppresses the proliferation of tumor cells (41)."
| 20 2

reach
"Firstly, we confirm the presence of the Usp12, Uaf-1, and WDR20 complex in PC cells and demonstrate the importance of Uaf-1 and WDR20 for Usp12 stabilisation."

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."

reach
"Overall, the UAF1, USP12, and WDR20 complex is distinguished from the two free USP12 structures and the two UAF1 and USP12 complex structures by the apparent stabilization of most flexible structural elements found in the DUB enzyme."

reach
"Overall these results highlight the potential importance of the Usp12, Uaf-1, and WDR20 complex in AR regulation and PC progression."

reach
"Highlights : Androgen receptor is a key transcriptional regulator in prostate cancer Usp12, Uaf-1, and WDR20 complex plays a crucial role in androgen receptor stability and activity Destabilising an individual Usp12, Uaf-1, and WDR20 complex member reduces the protein levels of the whole complex and diminishes androgen receptor activity Protein levels of all members of the Usp12, Uaf-1, and WDR20 complex are significantly increased in PC INTRODUCTION."

reach
"During revision of this manuscript, a structure for the USP12, UAF1, and WDR20 complex was published."

sparser
"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center."

reach
"For example, silencing of USP12 cofactors, Usp1-associated factor 1 (UAF1), or WD repeat domain 20 (WDR20), could influence the UAF1/WDR20/USP12 complex, thus inhibiting USP12 activity and AR-mediated transcription, leading to attenuated colony formation and promoting apoptosis [105]."

reach
"The USP46-WDR48-WDR20 and the USP12-WDR48-WDR20 complex have a very comparable overall structure."

reach
"Olazabal-Herrero et al (88) revealed that WDR20 facilitates shuttling of the USP12/UAF1/WDR20 complex between the plasma membrane, cytoplasm and nucleus via the CRM1 pathway, which requires the N-terminal motif of USP12 and the novel NES of WDR20.7."
| 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 ]."
| 2

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pY701-STAT1."

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pSTAT1."

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 binds USP12 and F219. 1 / 1
| 1

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
| 1

sparser
"We confirmed the association of endogenous PHLPP1 with WDR48 and USP12 by immunoprecipitation with PHLPP1 antibody ( xref B )."
USP12 activates WDR48.
| 2 1
USP12 activates WDR48. 3 / 3
| 2 1

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."

sparser
"USP12 activates UAF1 at the biochemical level, causing the deubiquitination of Notch in cells and in vitro."

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)."
USP12 inhibits WDR48.
| 2
USP12 bound to WDR20 inhibits WDR48. 1 / 1
| 1

reach
"The partial overlap of the binding interfaces and the high affinity of WDR20 suggests that WDR20 binding to USP12 and UAF1 can either prevent binding of the second UAF1 molecule or it can actively compete out UAF1 if it is bound to the USP12 and UAF1 complex."
USP12 inhibits WDR48. 1 / 1
| 1

reach
"Our results with the F313V variant are consistent with the fact that the equivalent residue of USP12 (F262) mutated to alanine dramatically reduces UAF1-stimulated catalysis of ubiquitin–AMC (Li et al, 2016)."
USP12 deubiquitinates WDR48.
| 1
USP12 deubiquitinates WDR48. 1 / 1
| 1

reach
"Usp12 and Usp46 deubiquitinate both H2A and H2B and Uaf-1 is required for this reaction [XREF_BIBR]."
WDR20 affects USP12
16 | 9 62 22
WDR20 binds USP12.
16 | 39 11
16 | 18 4

reach
"Usp12, Uaf-1 and WDR20 form a complex acting within a positive feedback loop in PC cells."

No evidence text available

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."

No evidence text available

No evidence text available

No evidence text available

reach
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."

No evidence text available

No evidence text available

No evidence text available
| 20 2

reach
"Firstly, we confirm the presence of the Usp12, Uaf-1, and WDR20 complex in PC cells and demonstrate the importance of Uaf-1 and WDR20 for Usp12 stabilisation."

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."

reach
"Overall, the UAF1, USP12, and WDR20 complex is distinguished from the two free USP12 structures and the two UAF1 and USP12 complex structures by the apparent stabilization of most flexible structural elements found in the DUB enzyme."

reach
"Overall these results highlight the potential importance of the Usp12, Uaf-1, and WDR20 complex in AR regulation and PC progression."

reach
"Highlights : Androgen receptor is a key transcriptional regulator in prostate cancer Usp12, Uaf-1, and WDR20 complex plays a crucial role in androgen receptor stability and activity Destabilising an individual Usp12, Uaf-1, and WDR20 complex member reduces the protein levels of the whole complex and diminishes androgen receptor activity Protein levels of all members of the Usp12, Uaf-1, and WDR20 complex are significantly increased in PC INTRODUCTION."

reach
"During revision of this manuscript, a structure for the USP12, UAF1, and WDR20 complex was published."

sparser
"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center."

reach
"For example, silencing of USP12 cofactors, Usp1-associated factor 1 (UAF1), or WD repeat domain 20 (WDR20), could influence the UAF1/WDR20/USP12 complex, thus inhibiting USP12 activity and AR-mediated transcription, leading to attenuated colony formation and promoting apoptosis [105]."

reach
"The USP46-WDR48-WDR20 and the USP12-WDR48-WDR20 complex have a very comparable overall structure."

reach
"Olazabal-Herrero et al (88) revealed that WDR20 facilitates shuttling of the USP12/UAF1/WDR20 complex between the plasma membrane, cytoplasm and nucleus via the CRM1 pathway, which requires the N-terminal motif of USP12 and the novel NES of WDR20.7."
| 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."
USP12 binds DMWD and WDR20. 1 / 1
| 1

sparser
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
| 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
"Both Usp12 and WDR20 alone were able to interact with both PHLPP (Figure xref ) and PHLPPL (Figure xref )."
WDR20 binds USP12 and 293 T. 1 / 1
| 1

reach
"We generated YFP-USP12 V279D/F287A and Myc-WDR20 F262A/W306A mutants and confirmed that these mutations largely or completely abrogate WDR20 binding to USP12 in 293 T cells ( Fig. 4 a)."
WDR20 activates USP12.
| 9 22 11
WDR20 activates USP12. 10 / 45
| 9 22 11

reach
"This is a result of enhanced activity of the endogenous Usp12 complex caused by increased levels of WDR20 which supports our data on the positive feedback loop within this complex."

sparser
"Based on our result, we propose a tenable model for USP12 activation by UAF1 and WDR20 ( xref )."

reach
"Importantly, by disrupting the interaction with WDR20, “NES” mutations abrogate WDR20-induced relocation of USP12 to the PM (Additional File 3), and would also prevent its full catalytic activation.Th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

eidos
"USP12 can be further activated by WDR20 [ 179,180 ] ."

reach
"Ning Zheng (USA) presented molecular studies of USP12, revealing that UAF1 and WDR20 potentiate USP12 catalytic activity."

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]."

eidos
"These results strongly suggest that WDR20 can activate USP12 by allosterically optimizing its catalytic cleft , whereas the effect of UAF1 binding cannot be directly transmitted to the catalytic cysteine through USP12 ."

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

reach
"First, our results rule out the possibility that UAF1 and WDR20 activate USP12 by enhancing its substrate affinity."

eidos
"This result clearly indicates that UAF1 and WDR20 allosterically activate USP12 through two distinct pathways ."
WDR20 decreases the amount of USP12.
| 1
WDR20 decreases the amount of USP12. 1 / 1
| 1

reach
"As Uaf-1 and WDR20 depletion reduces Usp12 levels their silencing has a comparable effect on the AR as the Usp12 depletion alone."
USP12 affects WDR20
16 | 40 11
USP12 binds WDR20.
16 | 39 11
16 | 18 4

reach
"Usp12, Uaf-1 and WDR20 form a complex acting within a positive feedback loop in PC cells."

No evidence text available

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."

No evidence text available

No evidence text available

No evidence text available

reach
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."

No evidence text available

No evidence text available

No evidence text available
| 20 2

reach
"Firstly, we confirm the presence of the Usp12, Uaf-1, and WDR20 complex in PC cells and demonstrate the importance of Uaf-1 and WDR20 for Usp12 stabilisation."

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."

reach
"Overall, the UAF1, USP12, and WDR20 complex is distinguished from the two free USP12 structures and the two UAF1 and USP12 complex structures by the apparent stabilization of most flexible structural elements found in the DUB enzyme."

reach
"Overall these results highlight the potential importance of the Usp12, Uaf-1, and WDR20 complex in AR regulation and PC progression."

reach
"Highlights : Androgen receptor is a key transcriptional regulator in prostate cancer Usp12, Uaf-1, and WDR20 complex plays a crucial role in androgen receptor stability and activity Destabilising an individual Usp12, Uaf-1, and WDR20 complex member reduces the protein levels of the whole complex and diminishes androgen receptor activity Protein levels of all members of the Usp12, Uaf-1, and WDR20 complex are significantly increased in PC INTRODUCTION."

reach
"During revision of this manuscript, a structure for the USP12, UAF1, and WDR20 complex was published."

sparser
"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center."

reach
"For example, silencing of USP12 cofactors, Usp1-associated factor 1 (UAF1), or WD repeat domain 20 (WDR20), could influence the UAF1/WDR20/USP12 complex, thus inhibiting USP12 activity and AR-mediated transcription, leading to attenuated colony formation and promoting apoptosis [105]."

reach
"The USP46-WDR48-WDR20 and the USP12-WDR48-WDR20 complex have a very comparable overall structure."

reach
"Olazabal-Herrero et al (88) revealed that WDR20 facilitates shuttling of the USP12/UAF1/WDR20 complex between the plasma membrane, cytoplasm and nucleus via the CRM1 pathway, which requires the N-terminal motif of USP12 and the novel NES of WDR20.7."
| 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."
USP12 binds DMWD and WDR20. 1 / 1
| 1

sparser
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
| 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
"Both Usp12 and WDR20 alone were able to interact with both PHLPP (Figure xref ) and PHLPPL (Figure xref )."
WDR20 binds USP12 and 293 T. 1 / 1
| 1

reach
"We generated YFP-USP12 V279D/F287A and Myc-WDR20 F262A/W306A mutants and confirmed that these mutations largely or completely abrogate WDR20 binding to USP12 in 293 T cells ( Fig. 4 a)."
USP12 activates WDR20.
| 1
USP12-C48S activates WDR20. 1 / 1
| 1

reach
"It was found that the mutant USP12-C48S, which was produced by replacing the cysteine active site (C48) of USP12 with serine (C48S), still could rescue mHTT-mediated toxicity in neurons and was unaffected by the knockdown of USP12 cofactors UAF-1 and WDR20 that important for USP12 activity."
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."
LuxY affects USP12
| 41
| 41

sparser
"As shown in Fig. 3 c, the ability of YFP-USP12 delMEIL mutant to relocate to the PM when co-expressed with Myc-WDR20 was virtually abrogated."

sparser
"In contrast, the YFP-USP12 ST/AA mutant still co-localized with Myc-WDR20 to the PM."

sparser
"Importantly, co-IP analysis ( Fig. 3 d) showed that YFP-USP12 delMEIL interacts with Myc-WDR20 as efficiently as wild type YFP-USP12."

sparser
"We generated YFP-USP12 V279D/F287A and Myc-WDR20 F262A/W306A mutants and confirmed that these mutations largely or completely abrogate WDR20 binding to USP12 in 293 T cells ( Fig. 4 a)."

sparser
"As shown in Fig. 4 b, YFP-USP12 V279D/F287A did not relocate to the PM when co-expressed with wild type Myc-WDR20, and conversely, co-expression with Myc-WDR20 F262A/W306A did not result in PM localiz[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As in 293 T cells, YFP-USP12 also localized to the PM in live HeLa cells when co-expressed with Myc-WDR20 ( Fig. 4 c)."

sparser
"The YFP-USP12 fluorescent signal was rapidly recovered in an area of the PM where it had been bleached."

sparser
"The calculated halftime of recovery (t 1/2 ) and mobile fraction (F m ) values were 19.44 s and 65.29%, respectively, indicating that the PM localization of YFP-USP12 is highly dynamic."

sparser
"The clearest and most statistically significant effect of LMB was on YFP-USP12 and, particularly, on YFP-WDR20, indicating that both proteins are actively exported from the nucleus by the CRM1-mediate[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Of note, YFP-USP12 and YFP-WDR20 were evenly distributed between nucleus and cytoplasm in LMB-treated cells, but they did not accumulate to a high level inside the nucleus."
USP12 affects AR
3 1 | 28 6
USP12 activates AR.
| 9 1
USP12 activates AR. 8 / 10
| 7 1

reach
"We have recently reported that Usp12, in combination with Uaf-1, can increase the transcriptional activity of AR [XREF_BIBR], and hence we wanted to analyse the importance of Akt phosphorylation sites in this process."

reach
"Also, USP12 co-localizes with AR in the cytoplasm and promotes AR transcriptional activity by confronting the ubiquitin dependent degradation of AR [XREF_BIBR]."

reach
"Deubiquitinating enzyme Usp12 is a novel co-activator of the androgen receptor."

reach
"This further confirms that each complex member alone has a limited effect on AR activity but in combination the Usp12 complex significantly increases AR transcriptional activity implying that targeting any of the binding partners should offer the same efficacy as targeting Usp12 alone."

sparser
"This data suggests that AR co-activation by Usp12 and Uaf-1 is largely driven through negating AR phosphorylation by Akt inactivation."

reach
"Our previous observations for the LNCaP cell line that express AR FL but not AR Vs have demonstrated that USP12 silencing causes a decrease in transcript expression of all the AR target genes [XREF_BIBR] supporting our data that AR Vs are not targeted by USP12 in the AR V expressing CWR22Rv1 cell line."

reach
"Interestingly, Usp12 and WDR20 alone significantly increased AR activity but this effect was greatest when Usp12, Uaf-1 and WDR20 were overexpressed simultaneously."

reach
"Cell lines used in this study express low levels of endogenous Usp12 and Uaf-1, consequently even without the addition of Uaf-1 overexpression of WDR20 alone was enough to significantly enhance the AR activity."
USP12 bound to WDR20 activates AR. 1 / 1
| 1

reach
"USP12 binds to Uaf-1 and WDR20 to form a complex to deubiquitinate AR, thereby increasing AR protein stability and transcriptional activity, while the depletion of WDR20 and Uaf-1 displays the opposite effect."
USP12 bound to WDR48 activates AR. 1 / 1
| 1

reach
"USP12 binds to Uaf-1 and WDR20 to form a complex to deubiquitinate AR, thereby increasing AR protein stability and transcriptional activity, while the depletion of WDR20 and Uaf-1 displays the opposite effect."
USP12 binds AR.
3 | 3 5
3 | 3 5

No evidence text available

sparser
"Although we were able to confirm the USP12- AR FL interaction we could not detect any interaction between USP12 and AR V7 (Figure xref )."

sparser
"To validate this result we overexpressed USP12 with AR FL, N-terminus of AR (AR ND) and AR N-terminus with DNA binding domain (AR ND-DNA BD) to localise the USP12-AR interaction."

sparser
"The requirement of the AR ligand binding domain to ensure an interaction between USP12 and AR is supported by our results in Figure xref showing that AR FL is stabilised following USP12 overexpression whereas the AR V7 proteins levels are unaffected (Figure xref )."

No evidence text available

reach
"To investigate if this was caused by the lack of interaction between AR and Usp12 in the absence of the specific serine residues, we overexpressed Usp12 alongside wild-type and mutant ARs followed by immunoprecipitation."

reach
"The requirement of the AR ligand binding domain to ensure an interaction between USP12 and AR is supported by our results in Figure XREF_FIG showing that AR FL is stabilised following USP12 overexpression whereas the AR V7 proteins levels are unaffected."

reach
"We have recently reported that Usp12, in complex with Uaf-1 and WDR20, can directly bind and deubiquitinate the AR resulting in increased receptor stability and transcriptional activity [XREF_BIBR]."

sparser
"To investigate if this was caused by the lack of interaction between AR and Usp12 in the absence of the specific serine residues, we overexpressed Usp12 alongside wild-type and mutant ARs followed by immunoprecipitation."

sparser
"Usp12 was capable of interacting with both AR S213A and AR S213A/S791A with comparable efficiency to wild-type confirming that these sites are not required for this interaction (Figure xref )."
USP12 deubiquitinates AR.
1 | 8
USP12 deubiquitinates AR. 8 / 8
1 | 7

reach
"USP12 binds to Uaf-1 and WDR20 to form a complex to deubiquitinate AR, thereby increasing AR protein stability and transcriptional activity, while the depletion of WDR20 and Uaf-1 displays the opposite effect."

"The <span class="match term1">AR</span> is known to be regulated by a number of post-translational modifications and we have recently identified the deubiquitinating enzyme <span class="match term0">Usp12</span> as a positive regulator of <span class="match term1">AR</span>"

reach
"We have recently reported that AR is deubiquitinated and stabilised by Usp12 resulting in increased transcriptional activity."

reach
"In this report we demonstrate that Usp12, in complex with Uaf-1 and WDR20, deubiquitinates the AR to enhance receptor stability and transcriptional activity."

reach
"We determined that Usp12 deubiquitinates the AR resulting in elevated receptor stability and activity."

reach
"We find that USP12 deubiquitinates MDM2 and AR, which in turn controls the levels of the TP53 tumour suppressor and AR oncogene in prostate cancer."

reach
"USP12 in the presence of its cofactors Uaf-1 and WDR20 deubiquitinates AR to enhance AR protein stability and transcriptional activity [71] USP12 in complex with Uaf-1 and WDR20 also abrogates phospho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 deubiquitinates AR on leucine. 1 / 1
| 1

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 inhibits AR.
| 2
USP12 inhibits AR. 2 / 3
| 2

reach
"USP12 inhibition in AR V positive lines drives the AR V expression profile."

reach
"Also, USP12 co-localizes with AR in the cytoplasm and promotes AR transcriptional activity by confronting the ubiquitin dependent degradation of AR [XREF_BIBR]."
USP12 dephosphorylates AR.
| 3
USP12 leads to the dephosphorylation of AR on S215. 3 / 3
| 3

reach
"In agreement with the above result, knockdown of Usp12 in LNCaP cells increased both AR S213 phosphorylation and AR turnover."

reach
"Our data demonstrates that Usp12 increases the levels of PHLPP and PHLPPL that in turn decreases the active pAkt pool and inhibits AR S213 phosphorylation by Akt."

reach
"As such, overexpressing Usp12 inhibits AR S213 phosphorylation resulting in increased AR stability and transcriptional activity."
USP12 increases the amount of AR.
| 2
USP12 increases the amount of AR. 2 / 2
| 2

reach
"Our previous observations for the LNCaP cell line that express AR FL but not AR Vs have demonstrated that USP12 silencing causes a decrease in transcript expression of all the AR target genes [XREF_BIBR] supporting our data that AR Vs are not targeted by USP12 in the AR V expressing CWR22Rv1 cell line."

reach
"Our data suggests that USP12 is unable to modulate AR V levels or activity but is capable of targeting AR FL."
USP12 ubiquitinates AR.
| 1
USP12 leads to the ubiquitination of AR. 1 / 1
| 1

reach
"Prior studies suggested a role of USP12 in prostate carcinomas, wherein USP12 promoted AR signalling and tumour cell proliferation, as well as therapy resistance, by regulating AR ubiquitination and MDM2-P53 signalling ."
USP12 affects PHLPP1
8 1 | 21 4
USP12 binds PHLPP1.
8 | 6 4
8 | 6 2

No evidence text available

reach
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs (XREF_FIG C)."

No evidence text available

No evidence text available

No evidence text available

sparser
"Additionally, Usp12 was predicted to interact with both of these phosphatases and a more recent report confirmed the interaction between Usp12 and PHLPP in colorectal cells [ xref ]."

No evidence text available

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]"

reach
"We demonstrated that Usp12, and two Usp12 interacting proteins, Uaf-1 and WDR20 [XREF_BIBR], [XREF_BIBR], form a complex with PHLPP and PHLPPL."

reach
"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 Maddik[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
| 1

sparser
"We confirmed the association of endogenous PHLPP1 with WDR48 and USP12 by immunoprecipitation with PHLPP1 antibody ( xref B )."
USP12 deubiquitinates PHLPP1.
1 | 8
USP12 deubiquitinates PHLPP1. 9 / 9
1 | 8

reach
"It is possible that USP12 may deubiquitinate and stabilize PHLPP only at higher cellular levels of USP12."

reach
"USP12 deubiquitinates AKT phosphatase PHLPP."

reach
"Further analysis using denaturing immunoprecipitation experiments revealed that Usp12 can also deubiquitinate and stabilise both PHLPP and PHLPPL."

reach
"The UAF1/USP12 complex deubiquitinates PHLPP1 and suppresses the proliferation of tumor cells (41)."

reach
"Usp12 deubiquitinates and stabilises PHLPP and PHLPPL and controls Akt activation status."

"USP11 stabilizes IKK-alpha to stabilize and activate p53"

reach
"The deubiquitinating enzyme Usp12 deubiquitinates and stabilizes PHLPP and PHLPPL."

reach
"Secondly, Usp12 deubiquitinates and stabilises PHLPP and PHLPPL proteins which enhances dephosphorylation and deactivation of Akt."

reach
"USP12-Uaf-1-WDR20 complex directly deubiquitinates and stabilizes PHLPP and PHLPPL, resulting in a decrease in the active p-Akt level."
USP12 inhibits PHLPP1.
| 3
USP12 inhibits PHLPP1. 3 / 3
| 3

reach
"Because PHLPP1 is a potent negative regulator of the PI3-kinase and Akt pathway, we hypothesized that WDR48 and USP12 might suppress Akt signaling by stabilizing PHLPP1."

reach
"Contrarily, a different study shows USP12 suppresses Akt-dependent cell growth of tumor cells by stabilizing tumor suppressor PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) [ 13 ]."

reach
"However, USP12 has also been shown to inhibit AKT-dependent cell survival by stabilizing the pro-apoptotic phosphatases PHLPP1 and/or PHLPPL ."
USP12 activates PHLPP1.
| 2
USP12 activates PHLPP1. 2 / 3
| 2

reach
"On the other hand, USP12 can also stabilize AR proteins and enhance their transcriptional activity by stabilizing the AKT (protein kinase B) dephosphorylases (PHLPP and PHLPPL) (McClurg et al., 2014)."

reach
"In fact, overexpression of WDR48 and USP12 induced apoptosis similarly to PHLPP1."
USP12 increases the amount of PHLPP1.
| 1
USP12 increases the amount of PHLPP1. 1 / 2
| 1

reach
"Our data demonstrates that Usp12 increases the levels of PHLPP and PHLPPL that in turn decreases the active pAkt pool and inhibits AR S213 phosphorylation by Akt."
USP12 ubiquitinates PHLPP1.
| 1
USP12 ubiquitinates PHLPP1. 1 / 1
| 1

reach
"Moreover, the WD repeat protein, WDR48, in complex with USP12 suppresses Akt signaling by deubiquitinating the PHLPP1 in colon carcinoma cells (HCT116)."
| 11 18
USP12 translocates from the cytoplasm to the nucleus. 10 / 11
| 4 7

sparser
"Furthermore, we found that in IFN signaling USP12 translocates from the cytoplasm to the nucleus."

sparser
"USP12 translocates from the cytoplasm to the nucleus in IFN signaling."

reach
"Mechanistically, USP12 translocates from the cytoplasm to the nucleus and blocks the CREB-binding protein (CBP)-induced acetylation of phosphorylated STAT1 (p-STAT1), thereby maintaining the nuclear p-STAT1 levels and IFN antiviral activity [21]."

sparser
"To our surprise, we observed that during mIFNβ treatment, cytoplasmic USP12 protein levels dramatically decreased and nuclear USP12 protein levels increased accordingly ( xref ), suggesting that USP12 translocates from the cytoplasm to the nucleus in IFN signaling."

sparser
"For example, USP12 is described above as promoting NF-κB activation for NLRP3 inflammatory microsome production, but in NSCLC it inhibits NF-κB signaling activity and regulates chemokine secretion by deubiquitinating and stabilizing PPM1B. Apart from that, USP12 can translocate from the cytoplasm to the nucleus during signaling to function in maintaining nuclear p-STAT1 levels and IFN antiviral efficacy."

reach
"Apart from that, USP12 can translocate from the cytoplasm to the nucleus during signaling to function in maintaining nuclear p-STAT1 levels and IFN antiviral efficacy."

reach
"The recent studies showed that USP12 translocated from the cytoplasm to the nucleus in IFN signaling [ 18 ]."

sparser
"To our surprise, in IFN signaling USP12 translocates from the cytoplasm to the nucleus."

sparser
"Mechanistically, USP12 translocates from the cytoplasm to the nucleus and blocks the CREB-binding protein (CBP)-induced acetylation of phosphorylated STAT1 (p-STAT1), thereby maintaining the nuclear p-STAT1 levels and IFN antiviral activity [ xref ]."

sparser
"The recent studies showed that USP12 translocated from the cytoplasm to the nucleus in IFN signaling [ 18 ]."
USP12 translocates from the nucleus to the cytoplasm. 6 / 6
| 6

sparser
"After stimulating the TCR with an anti-CD3 antibody, phosphorylation of the USP12 cytoplasmic pool could be induced, allowing USP12 to translocate from the nucleus to the cytoplasm and acted directly on the substrate proteins LAT and Trat1 to stabilize the TCR complex on the T cell surface during signaling."

sparser
"However, in TCR signaling, the translocation manner was quite different that USP12 translocated from the nucleus to the cytoplasm to deubiquitinate LAT and Trat1 proteins [ 20 ]."

sparser
"A recent report showed that in TCR signaling, USP12 translocates from the nucleus to the cytoplasm, where USP12 deubiquitinates and stabilizes LAT and Trat1 and prevents their lysosome-dependent degradation in T cells."

sparser
"It has been reported that in TCR signaling, USP12 translocates from the nucleus to the cytoplasm to deubiquitinate LAT and Trat1 proteins [ xref ]."

sparser
"Together with the recent finding that USP12 can be exported from the nucleus to the cytoplasm by CRM1 ( Jahan et al., 2016 ), our results raised the possibility that the USP12/WDR20 complex may underg[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"However, in the TCR-related studies, anti-CD3 stimulation of the TCR translocated USP12 from the nucleus to the cytoplasm to act on the substrate proteins LAT and Trat1 to stabilize the TCR."
USP12 translocates to the nucleus. 5 / 5
| 3 2

sparser
"USP12 translocates into the nucleus in IFN signaling, which critically regulates nuclear p-STAT1 levels and IFN antiviral activity by inhibiting CBP’s acetyltransferase activity."

reach
"Moreover, USP12, which is a cell-intrinsic inhibitor of the acetyltransferase, CBP, translocates into the nucleus and regulates the nuclear-p-STAT1-mediated antiviral response independent of its deubiquitinase activity [21]."

reach
"Further investigations are required to elucidate how USP12 is translocated to the nucleus."

sparser
"Given that we have demonstrated that USP12 translocates into the nucleus in IFN signaling, we next sought to determine whether USP12 regulates p-STAT1 levels through CBP."

reach
"Lehoux et al., found that USP12 and USP46 fused to red fluorescent protein were predominantly cytoplasmic in C33A cervical carcinoma cells, but were recruited to the nucleus via an interaction with the HPV E1 helicase [XREF_BIBR]."
USP12 translocates from the nucleus to the cytosol. 4 / 4
| 2 2

sparser
"Stimulation with anti-CD3 resulted in phosphorylation and time-dependent translocation of Usp12 from the nucleus to the cytosol."

reach
"Usp12 could translocate from the nucleus to the cytosol on TCR stimulation, and this relocalization process requires one or more kinases like phosphatase enzymes [45]."

sparser
"Usp12 could translocate from the nucleus to the cytosol on TCR stimulation, and this relocalization process requires one or more kinases like phosphatase enzymes [ xref ]."

reach
"Stimulation with anti-CD3 resulted in phosphorylation and time dependent translocation of Usp12 from the nucleus to the cytosol."
USP12 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]"
USP12 translocates from the nucleus. 1 / 1
| 1

reach
"However, in TCR signaling, the translocation manner was quite different that USP12 translocated from the nucleus to the cytoplasm to deubiquitinate LAT and Trat1 proteins [ 20 ]."
USP12 affects PHLPP2
4 1 | 14 3
USP12 binds PHLPP2.
4 | 3 3
4 | 3 2

reach
"Here we report that Usp12, in complex with Uaf-1 and WDR20, interacts with PHLPP and PHLPPL in PC cells resulting in their deubiquitination and protein stabilisation."

No evidence text available

reach
"We demonstrated that Usp12, and two Usp12 interacting proteins, Uaf-1 and WDR20 [XREF_BIBR], [XREF_BIBR], form a complex with PHLPP and PHLPPL."

sparser
"The Usp12 complex interacts with PHLPP and PHLPPL."

sparser
"In agreement with the previous study, we found that both PHLPP (Figure xref ) and PHLPPL (Figure xref ) interacted with Usp12."

No evidence text available

No evidence text available

reach
"In agreement with the previous study, we found that both PHLPP and PHLPPL interacted with Usp12."

No evidence text available
| 1

sparser
"Both Usp12 and WDR20 alone were able to interact with both PHLPP (Figure xref ) and PHLPPL (Figure xref )."
USP12 deubiquitinates PHLPP2.
1 | 7
USP12 deubiquitinates PHLPP2. 7 / 7
1 | 6

reach
"Usp12 deubiquitinates and stabilises PHLPP and PHLPPL and controls Akt activation status."

"we demonstrate that <span class="match term0">Usp12</span>, in complex with Uaf-1 and WDR20, directly deubiquitinates and stabilises the Akt phosphatases PHLPP and <span class="match term1">PHLPPL</span> resulting in decreased levels of active pAkt."

reach
"Further analysis using denaturing immunoprecipitation experiments revealed that Usp12 can also deubiquitinate and stabilise both PHLPP and PHLPPL."

reach
"Secondly, Usp12 deubiquitinates and stabilises PHLPP and PHLPPL proteins which enhances dephosphorylation and deactivation of Akt."

reach
"The deubiquitinating enzyme Usp12 deubiquitinates and stabilizes PHLPP and PHLPPL."

reach
"USP12-Uaf-1-WDR20 complex directly deubiquitinates and stabilizes PHLPP and PHLPPL, resulting in a decrease in the active p-Akt level."

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 deubiquitinates PHLPP2 on leucine. 1 / 1
| 1

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 increases the amount of PHLPP2.
| 2
USP12 increases the amount of PHLPP2. 1 / 2
| 1

reach
"Our data demonstrates that Usp12 increases the levels of PHLPP and PHLPPL that in turn decreases the active pAkt pool and inhibits AR S213 phosphorylation by Akt."
Modified USP12-C48A increases the amount of PHLPP2. 1 / 1
| 1

reach
"Importantly, overexpression of Usp12 deubiquitinated both PHLPP and PHLPPL and this elevated the steady-state levels of the enzymes, while overexpression of an enzymatically inactive Usp12 C48A mutant failed to elevate PHLPP and PHLPPL levels suggesting the importance of Usp12 enzymatic activity for phosphatase regulation."
USP12 activates PHLPP2.
| 1
USP12 activates PHLPP2. 1 / 2
| 1

reach
"On the other hand, USP12 can also stabilize AR proteins and enhance their transcriptional activity by stabilizing the AKT (protein kinase B) dephosphorylases (PHLPP and PHLPPL) (McClurg et al., 2014)."
USP12 inhibits PHLPP2.
| 1
USP12 inhibits PHLPP2. 1 / 1
| 1

reach
"However, USP12 has also been shown to inhibit AKT-dependent cell survival by stabilizing the pro-apoptotic phosphatases PHLPP1 and/or PHLPPL ."
WDR48 affects WDR20
| 20 3
| 20 2

reach
"Firstly, we confirm the presence of the Usp12, Uaf-1, and WDR20 complex in PC cells and demonstrate the importance of Uaf-1 and WDR20 for Usp12 stabilisation."

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."

reach
"Overall, the UAF1, USP12, and WDR20 complex is distinguished from the two free USP12 structures and the two UAF1 and USP12 complex structures by the apparent stabilization of most flexible structural elements found in the DUB enzyme."

reach
"Overall these results highlight the potential importance of the Usp12, Uaf-1, and WDR20 complex in AR regulation and PC progression."

reach
"Highlights : Androgen receptor is a key transcriptional regulator in prostate cancer Usp12, Uaf-1, and WDR20 complex plays a crucial role in androgen receptor stability and activity Destabilising an individual Usp12, Uaf-1, and WDR20 complex member reduces the protein levels of the whole complex and diminishes androgen receptor activity Protein levels of all members of the Usp12, Uaf-1, and WDR20 complex are significantly increased in PC INTRODUCTION."

reach
"During revision of this manuscript, a structure for the USP12, UAF1, and WDR20 complex was published."

sparser
"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center."

reach
"For example, silencing of USP12 cofactors, Usp1-associated factor 1 (UAF1), or WD repeat domain 20 (WDR20), could influence the UAF1/WDR20/USP12 complex, thus inhibiting USP12 activity and AR-mediated transcription, leading to attenuated colony formation and promoting apoptosis [105]."

reach
"The USP46-WDR48-WDR20 and the USP12-WDR48-WDR20 complex have a very comparable overall structure."

reach
"Olazabal-Herrero et al (88) revealed that WDR20 facilitates shuttling of the USP12/UAF1/WDR20 complex between the plasma membrane, cytoplasm and nucleus via the CRM1 pathway, which requires the N-terminal motif of USP12 and the novel NES of WDR20.7."
| 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 )."

reach
"It has been mentioned previously that USP12 silencing inhibits PC cell proliferation, induces cell cycle arrest, and promotes apoptosis [42]."

reach
"Therefore, it can be inferred that USP12 can promote the proliferation of PCa cells."

reach
"Depletion of USP12 decreased PC cell proliferation, increased apoptosis and caused G 1 arrest ( Burska et al., 2013 and McClurg et al., 2014 )."

reach
"In vitro experiments in HCC cell lines showed that USP12 knockdown inhibited cell proliferation through G2/M arrest."

reach
"Knockdown of USP12 inhibited HCC cell proliferation and promoted apoptosis via the p38-MAPK pathway."

reach
"CCK8 assays showed that deletion of USP12 inhibited gastric cancer cell proliferation (Fig. 2B, C)."

reach
"Previous studies show that USP12 promotes the growth of multiple myeloma (MM) cells and USP12 knockdown significantly inhibits cell proliferation."

reach
"By the CCK8 assay, it was observed that the proliferation of gastric cancer cells was suppressed by USP12 deletion, and this inhibition was partially mitigated by YAP overexpression (Fig. 5D)."

reach
"In addition, USP12 activates CD4 + T cell proliferation by stabilizing BCL10 and targeting the NF-κB signaling pathway."

reach
"On the other hand, USP12 promoted prostate cancer (PC) cells proliferation by forming a complex with Uaf-1 and WDR20 and deubiquitinating AR, thereby increasing AR stability and transcriptional activity, whereas USP12 silencing led to a significant decrease in PC cell proliferation [42, 64]."

reach
"As shown in XREF_FIG B, knockdown of WDR48 and USP12 by shRNA accelerated the rate of cell proliferation compared with control shRNA transfected cells."

reach
"In contrast, overexpression of WDR48 and USP12 (XREF_FIG C) suppressed cell proliferation similarly to PHLPP1 (XREF_FIG D)."

reach
"Furthermore, PI staining by flow cytometry analysis revealed that USP12 deletion significantly increased G0/G1 phase cell proliferation (Fig. 2H–K)."

reach
"We further established that Usp12 depletion reduced PC cell proliferation and induced apoptosis, furthermore Usp12 levels are increased in PC tissue [XREF_BIBR]."

reach
"Over-expression of USP12 induced apoptosis and suppressed the proliferation of HCT116 cells ( Gangula and Maddika, 2013 )."

reach
"Several studies reported the effects of USP12 on cell phenotypes, and we give a summary of the roles and mechanisms of USP12 in tumorigenesis in the following part.The overexpression of USP12 in human colorectal cancer cells was previously found to inhibit cell proliferation, and siUSP12 could reverse this effect [63]."

reach
"As a result, depleting Usp12 decreased PC cellular proliferation and increased cellular apoptosis suggesting it may be a potential target for CRPC therapy [XREF_BIBR]."
USP12 affects EP300
2 | 1 15 2
USP12 binds EP300.
2 | 1 2
2 | 1 2

sparser
"Therefore, we observed whether there was interaction between the USP12 protein and p300 protein."

No evidence text available

No evidence text available

sparser
"Mechanically, USP12 bind to p300 protein and inhibited its degradation, thus promoting the transcription of METTL3."

reach
"Mechanically, USP12 bind to p300 protein and inhibited its degradation, thus promoting the transcription of METTL3."
USP12 deubiquitinates EP300.
| 1 3
USP12 deubiquitinates EP300. 4 / 4
| 1 3

trips
"De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced Cardiac Hypertrophy."

reach
"Third, the knockdown of USP12 significantly increased levels of p300 ubiquitination, whereas overexpression of USP12 reduced p300 ubiquitination."

reach
"USP12 deubiquitinated p300 to activate the transcription of methyltransferase-like 3 (METTL3), which resulted in the abnormal m6A RNA methylation in cardiomyocyte and exacerbated cardiac hypertrophy (Ref."

reach
"Next, we tested whether USP12 inhibited the ubiquitination of p300."
USP12 decreases the amount of EP300.
| 4
USP12 decreases the amount of EP300. 4 / 4
| 4

reach
"Second, MG132 treatment, the inhibitor of proteasome, restored silencing USP12-induced downregulation of p300 protein level in NRCMs."

reach
"Third, the knockdown of USP12 significantly increased levels of p300 ubiquitination, whereas overexpression of USP12 reduced p300 ubiquitination."

reach
"As showed in Fig. 5 H, overexpression of USP12 reduced the ubiquitination level of p300."

reach
"But, inhibition of USP12 increased the ubiquitination level of p300 ( Fig. 5 I)."
USP12 activates EP300.
| 4
USP12 activates EP300. 4 / 4
| 4

reach
"According to a recent study, USP12 (ubiquitin-specific protease 12) via enhancing p300/MTLL3 axis promote myocardial hypertrophy [61], and our finding may indicate the possibility of m A methylation and ubiquitination cooperatively regulate heart growth."

reach
"These data indicated that USP12 blocked p300 degradation and stabilized p300 protein.Many studies have demonstrated that USP12 plays a role in stabilizing protein by binding to the substrate and inhib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Further, we demonstrated that USP12 positively regulated p300, a methyltransferase which could promote H3K27 acetylation in the promoter of METTL3 and induce METTL3 transcription [ 24 ]."

reach
"First, USP12 can prolong the half-life of p300 protein."
USP12 increases the amount of EP300.
| 2
USP12 increases the amount of EP300. 2 / 2
| 2

reach
"Our result showed that inhibition of USP12 decreased the protein expression of p300 and reduced the transcription activity of METTL3 promoter ( Fig. 4 C–D)."

reach
"Furthermore, Lu et al. found that USP12 enhances the p300 expression, leading to increased METTL3 expression."
USP12 ubiquitinates EP300.
| 1
USP12 leads to the ubiquitination of EP300. 1 / 1
| 1

reach
"Third, the knockdown of USP12 significantly increased levels of p300 ubiquitination, whereas overexpression of USP12 reduced p300 ubiquitination."
USP12 affects CREBBP
| 3 15 1
USP12 binds CREBBP.
| 15 1
| 9

sparser
"Thus, we further confirmed the interaction between USP12 and CBP."

sparser
"Moreover, we demonstrated that in IFN signaling, USP12 interacted with CBP but not with either p-STAT1 or TCPTP ( xref ), suggesting that USP12 affects the p-STAT1 and TCPTP interaction through targeting CBP."

sparser
"Together, these findings demonstrated that USP12 constitutively binds with CBP in cells."

sparser
"In bone marrow-derived macrophages (BMDMs) isolated from mice and RAW264.7 cells, endogenous USP12 also interacted with endogenous CBP ( xref )."

sparser
"Importantly, USP12 constitutively binds with CBP in mouse primary lung and liver cells ( xref )."

sparser
"The results showed that endogenous USP12 interacted with endogenous CBP in intact cells, and IFNα treatment promoted USP12 nuclear accumulation ( xref and xref )."

sparser
"In our mass spectroscopy analysis, we noticed an interaction between USP12 and CBP."

sparser
"We also demonstrated that USP12 interacted with CBP, but not either p-STAT1 or TCPTP, suggesting that the regulation of USP12 on both TCPTP binding and p-STAT1 levels is through CBP."

sparser
"USP12 interacts with CBP and blocks the acetyltransferase activity of CBP."
| 6

sparser
"In this study, we demonstrated that USP12 can bind with the HAT domain of CBP in vivo and in vitro ."

sparser
"Taken together, these findings suggest that USP12 binds to the HAT domain of CBP and blocks CBP’s acetyltransferase activity in cells."

sparser
"Interestingly, USP12 can interact with the HAT domain of CBP."

sparser
"The aforementioned results demonstrated that USP12 binds to the HAT domain of CBP and blocks CBP’s acetylation action."

sparser
"Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP’s acetyltransferase activity."

sparser
"In vitro binding assay further demonstrated that USP12 binds with the HAT domain of CBP ( xref )."
USP12 binds CREBBP. 1 / 1
| 1

isi
"Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP's acetyltransferase activity."
USP12 deacetylates CREBBP.
| 2
USP12 leads to the deacetylation of CREBBP. 2 / 2
| 2

reach
"Additionally, another study has demonstrated that USP12 can inhibit CREB-binding protein (CBP)-mediated acetylation in cells in a non-catalytic manner."

reach
"Additionally, another study has demonstrated that USP12 can inhibit CREB-binding protein (CBP)-mediated acetylation in cells in a non-catalytic manner."
USP12 inhibits CREBBP.
| 1
USP12 inhibits CREBBP. 1 / 1
| 1

reach
"In addition, as the nuclear USP12 inhibited the acetyltransferase activity of CBP and regulated the p-STAT1-mediated IFN antiviral response [21]."
PHLPP1 affects USP12
8 | 6 4
8 | 6 2

No evidence text available

reach
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs (XREF_FIG C)."

No evidence text available

No evidence text available

No evidence text available

sparser
"Additionally, Usp12 was predicted to interact with both of these phosphatases and a more recent report confirmed the interaction between Usp12 and PHLPP in colorectal cells [ xref ]."

No evidence text available

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]"

reach
"We demonstrated that Usp12, and two Usp12 interacting proteins, Uaf-1 and WDR20 [XREF_BIBR], [XREF_BIBR], form a complex with PHLPP and PHLPPL."

reach
"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 Maddik[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
| 1

sparser
"We confirmed the association of endogenous PHLPP1 with WDR48 and USP12 by immunoprecipitation with PHLPP1 antibody ( xref B )."
USP12 affects autophagy
| 2 16
USP12 activates autophagy.
| 2 15
| 2 15

reach
"Usp12 induction of autophagy is a potential mechanism by which Usp12 confers neuroprotection in HD models."

reach
"Publisher Correction : Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington 's disease."

eidos
"Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy ."

reach
"Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1."

reach
"Another possibility is that Usp12 stimulation of autophagy confers neuroprotection primarily by clearing cargo other than mHTT."

reach
"Usp12 stimulation of autophagy, in the context of mHTT, could lead to more efficient cargo loading in autophagosomes, and thereby reduce mHTT associated toxicity."

reach
"Both alpha-synuclein and TDP-43 are substrates for autophagic degradation XREF_BIBR, XREF_BIBR, XREF_BIBR, and so, we might predict that stimulation of autophagy by Usp12 overexpression would also be neuroprotective in the related PD and ALS neuron models."

reach
"USP12 also non-catalytically induces cell autophagy in Huntington’s disease ."

reach
"Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington 's disease."

reach
"Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy."
USP12 inhibits autophagy.
| 1
| 1

reach
"Following studies by Aron et al. demonstrated that USP12 suppresses the toxicity of these mutated proteins by inducing autophagy in neurons."
USP12 affects IFI16
| 15 3
USP12 deubiquitinates IFI16.
| 8
USP12 deubiquitinates IFI16. 8 / 8
| 8

reach
"In this study, we found that USP12 significantly inhibited IFI16 ubiquitination and degradation, stabilized and extended the half-life of IFI16, and subsequently induced the STING-dependent expressions of IFN-β, CCL-5, IL-6, and downstream ISGs, which makes the host more resistant to DNA virus (S11 Fig)."

reach
"Our results showed that USP12 inhibited IFI16 ubiquitination and degradation through its deubiquitinase activity, thereby promoting IFI16-STING mediated antiviral response."

reach
"However, USP12 may positively regulate the IFI16-STING-mediated IFN-I antiviral response by deubiquitinating and stabilizing IFI16."

reach
"[56] USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16 [31]."

reach
"USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16."

reach
"Correction: USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16."

reach
"These results demonstrated that USP12 deubiquitinates and stabilizes IFI16 during DNA virus infection."

reach
"We found that USP12, but not USP12 , reduced the IFI16 degradation rate (Fig 6A) and ubiquitination level (Fig 6B) in HEK293T cells, which indicated that USP12 stabilized IFI16 and reversed IFI16 ubiquitination by its deubiquitinase activity."
USP12 activates IFI16.
| 4
USP12 activates IFI16. 4 / 4
| 4

reach
"These findings promote the understanding of varied regulation of USP12 in antiviral signaling.In summary, we reported that USP12 promoted IFI16-mediated innate antiviral signaling."

reach
"Fu et al. [49] discovered that USP12 promoted IFI16-mediated innate antiviral signaling."

reach
"By contrast, USP12 enhanced IFN-β, NF-κB, and ISRE promoter activities in a dose-dependent manner after cotransfection with IFI16 (Fig 4B)."

reach
"Notably, USP12-mediated ISG response was independent of IFI16 as either IFI16 deficiency in BMDMs or overexpression in Usp12 BMDMs had no impact on ISG transcription."
USP12 inhibits IFI16.
| 3
USP12 inhibits IFI16. 3 / 3
| 3

reach
"Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity, thereby maintaining IFI16 stability and promoting IFI16-STING-IRF3- and p65-mediated antiviral signaling."

reach
"Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity."

reach
"We found that USP12 deficiency promoted the degradation of IFI16 (Fig 5E)."
USP12 binds IFI16.
| 3
| 3

sparser
"The results showed that the endogenous USP12 formed a stable complex with IFI16 in BMDMs ( xref )."

sparser
"Immunoprecipitation and immunoblot assays were performed to validate whether USP12 interacts with IFI16."

sparser
"Similarly, USP12 interacted with IFI16 in HEK293 cells ( xref )."
USP12 affects BAX
4 | 6 7
4 | 6 7

reach
"The binding of USP12 to Bax shows the interaction as a DUB, which regulates ubiquitination on Bax."

reach
"We confirmed the interaction between USP12 and Bax via binding and GST pull-down assays."

sparser
"The binding of USP12 to Bax shows the interaction as a DUB, which regulates ubiquitination on Bax."

sparser
"USP12 silencing could induce the upregulation of Bax in prostate cancer by regulating the TP53 signaling pathway [ xref ], and in Hela cells, Bax could bind to USP12 in the nucleus [ xref ]."

reach
"The diverse regulation of cell proliferation and cell cycle by USP12 indicates its functional diversity and deserves further study.USP12 silencing could induce the upregulation of Bax in prostate cancer by regulating the TP53 signaling pathway [68], and in Hela cells, Bax could bind to USP12 in the nucleus [50]."

sparser
"We confirmed the interaction between USP12 and Bax via binding and GST pull-down assays."

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP12 affects METTL3
| 1 12 3
USP12 increases the amount of METTL3.
| 8
USP12 increases the amount of METTL3. 8 / 8
| 8

reach
"But the regulatory mechanism of METTL3 in Ang II-induced hypertrophic cardiomyocytes is still unclear.In this study, we demonstrated that the expression level of USP12 was increased in hypertrophic he[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Overexpressing USP12 increased the mRNA and protein expression of METTL3, as well as MAP3K6 and MAPK14 ( Fig. 3 D and E, Supplementary Fig. 3C and D )."

reach
"For example, USP12 overexpression could exacerbate Ang II-induced cardiac hypertrophy by raising the METTL3 level [51]."

reach
"Therefore, we speculated that USP12 enhanced METTL3 expression via p300."

reach
"On the other hand, we transfected the shRNA adenovirus targeting p300 into cells overexpressing USP12 to knock down p300, and we found that reducing p300 attenuated the increase of METTL3 expression a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Indeed, silencing USP12 inhibited the expression of METTL3, overexpression of USP12 enhanced METTL3."

reach
"In addition, we verified that p300 is the key for USP12-mediated enhancement of METTL3, as overexpression of p300 rescued the decrease of METTL3 expression in USP12-silenced NRCMs, while reducing p300[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"USP12 deubiquitinated p300 to activate the transcription of methyltransferase-like 3 (METTL3), which resulted in the abnormal m6A RNA methylation in cardiomyocyte and exacerbated cardiac hypertrophy (Ref."
USP12 binds METTL3.
| 1 3
| 1 3

sparser
"Co-immunoprecipitation (co-IP) result suggested that there was no interaction between USP12 and METTL3 under the stimulation of Ang II ( Supplementary Fig. 4A )."

sparser
"However, the result of co-IP assay showed that USP12 did not interact with METTL3, indicating that there was a transcriptional regulatory mechanism between USP12 and METTL3."

reach
"Thus, we detected whether there was an interaction between USP12 and METTL3."

sparser
"Thus, we detected whether there was an interaction between USP12 and METTL3."
USP12 activates METTL3.
| 1 2
USP12 activates METTL3. 3 / 3
| 1 2

reach
"Indeed, silencing USP12 inhibited the expression of METTL3, overexpression of USP12 enhanced METTL3."

eidos
"Furthermore , we discover that USP12 promote the expression of METTL3 via upregulating p300 ."

reach
"What's more, the luciferase reporter gene assay showed that silencing USP12 inhibited the transcription activity of METTL3 promoter ( Supplementary Fig. 4D ), while overexpressing USP12 promoted the t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 decreases the amount of METTL3.
| 1
USP12 bound to EP300 decreases the amount of METTL3. 1 / 1
| 1

reach
"Mechanically, USP12 bind to p300 protein and inhibited its degradation, thus promoting the transcription of METTL3."
USP12 affects HMGB1
4 | 1 9 2
USP12 binds HMGB1.
4 | 1 2
4 | 1 2

reach
"Recently, it was reported that USP12, another USP family member, is highly expressed in multiple myeloma cells and binds to HMGB1 to deubiquitinate and stabilize HMGB1, resulting in the promotion of pro-survival autophagy in myeloma (Li et al. 2022)."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"In the context of autophagy, the study of multiple myeloma (MM) showed that USP12 could interact with the key autophagy mediator HMGB1 (high mobility group box-1) protein to deubiquitinate and stabilize it [ xref ]."

sparser
"This suggests that targeting the USP12-HMGB1 axis could have therapeutic potential in human myeloma [ 80 ] ( Fig. 2 A)."
USP12 deubiquitinates HMGB1.
| 4
USP12 deubiquitinates HMGB1. 4 / 4
| 4

reach
"Recently, it was reported that USP12, another USP family member, is highly expressed in multiple myeloma cells and binds to HMGB1 to deubiquitinate and stabilize HMGB1, resulting in the promotion of pro-survival autophagy in myeloma (Li et al. 2022)."

reach
"Ubiquitin-specific protease-12 (USP12) interacts with deubiquitylated and stabilized HMGB1, promoting autophagy and conferring bortezomib resistance in myeloma cell lines."

reach
"USP12 emerges as a critical regulator in this context, interacting with and deubiquitinating the autophagy mediator, high mobility group box-1 (HMGB1)."

reach
"56 In multiple myeloma, the deubiquitination enzyme USP12 deubiquitinates HMGB1 and increase its stability, thus promoting autophagy."
USP12 increases the amount of HMGB1.
| 3
USP12 increases the amount of HMGB1. 3 / 3
| 3

reach
"Knockdown of USP12 decreased the level of HMGB1 and suppressed HMGB1-mediated autophagy in MM."

reach
"The knockdown of USP12 decreases HMGB1 levels, curtails autophagy, and consequently boosts MM cell susceptibility to BTZ [202]."

reach
"USP12 high expression promotes HMGB1 expression to induce autophagy and drug resistance in MM cells."
USP12 activates HMGB1.
| 1 1
USP12 activates HMGB1. 2 / 2
| 1 1

reach
"Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1."

eidos
"Knockdown of USP12 decreased the level of HMGB1 and suppressed HMGB1-mediated autophagy in MM ."
CREBBP affects USP12
| 15 1
| 9

sparser
"Thus, we further confirmed the interaction between USP12 and CBP."

sparser
"Moreover, we demonstrated that in IFN signaling, USP12 interacted with CBP but not with either p-STAT1 or TCPTP ( xref ), suggesting that USP12 affects the p-STAT1 and TCPTP interaction through targeting CBP."

sparser
"Together, these findings demonstrated that USP12 constitutively binds with CBP in cells."

sparser
"In bone marrow-derived macrophages (BMDMs) isolated from mice and RAW264.7 cells, endogenous USP12 also interacted with endogenous CBP ( xref )."

sparser
"Importantly, USP12 constitutively binds with CBP in mouse primary lung and liver cells ( xref )."

sparser
"The results showed that endogenous USP12 interacted with endogenous CBP in intact cells, and IFNα treatment promoted USP12 nuclear accumulation ( xref and xref )."

sparser
"In our mass spectroscopy analysis, we noticed an interaction between USP12 and CBP."

sparser
"We also demonstrated that USP12 interacted with CBP, but not either p-STAT1 or TCPTP, suggesting that the regulation of USP12 on both TCPTP binding and p-STAT1 levels is through CBP."

sparser
"USP12 interacts with CBP and blocks the acetyltransferase activity of CBP."
| 6

sparser
"In this study, we demonstrated that USP12 can bind with the HAT domain of CBP in vivo and in vitro ."

sparser
"Taken together, these findings suggest that USP12 binds to the HAT domain of CBP and blocks CBP’s acetyltransferase activity in cells."

sparser
"Interestingly, USP12 can interact with the HAT domain of CBP."

sparser
"The aforementioned results demonstrated that USP12 binds to the HAT domain of CBP and blocks CBP’s acetylation action."

sparser
"Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP’s acetyltransferase activity."

sparser
"In vitro binding assay further demonstrated that USP12 binds with the HAT domain of CBP ( xref )."
USP12 binds CREBBP. 1 / 1
| 1

isi
"Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP's acetyltransferase activity."
| 1 14
| 1 8

reach
"As a result, depleting Usp12 decreased PC cellular proliferation and increased cellular apoptosis suggesting it may be a potential target for CRPC therapy [XREF_BIBR]."

reach
"In this study, we identified significant upregulation of the m 6 A methyltransferase METTL3 (methyltransferase-like 3), the m 6 A reader protein YTHDF1 (YTH N6-methyladenosine RNA binding protein 1), as well as increased expression levels of USP12 (ubiquitin-specific peptidase 12), FOXO3 (forkhead box O3), and key molecules in the intrinsic apoptotic pathway, PUMA (p53 upregulated modulator of apoptosis) and BAX (Bcl-2-associated X), through proteomic profiling in an LPS (Lipopolysaccharide)-induced SIMD mouse model."

reach
"It has been mentioned previously that USP12 silencing inhibits PC cell proliferation, induces cell cycle arrest, and promotes apoptosis [42]."

reach
"Thus, these results suggest that WDR48 and USP12 negatively regulate Akt signaling and thereby induce apoptosis in conjunction with PHLPP1."

reach
"Invivo experiments showed that USP12-knockdown could suppress tumor growth in mice, and immuno blotting revealed that USP12 could induce G2/M arrest through the cyclin dependent kinase1 and cyclinB1 axis, and trigger apoptosis via the p38 and mitogen activated protein kinase pathway."

reach
"Over-expression of USP12 induced apoptosis and suppressed the proliferation of HCT116 cells ( Gangula and Maddika, 2013 )."

reach
"WDR48 and USP12 Negatively Regulate Akt Signaling and Promote Apoptosis."

eidos
"In vivo experiments showed that USP12-knockdown could suppress tumor growth in mice , and immuno-blotting revealed that USP12 could induce G2 / M arrest through the cyclin dependent kinase 1 / cyclinB1 axis , and trigger apoptosis via the p38 / mitogen-activated protein kinase pathway ."

reach
"In fact, overexpression of WDR48 and USP12 induced apoptosis similarly to PHLPP1."
| 6

reach
"Knockdown of USP12 inhibited HCC cell proliferation and promoted apoptosis via the p38-MAPK pathway."

reach
"We further established that Usp12 depletion reduced PC cell proliferation and induced apoptosis, furthermore Usp12 levels are increased in PC tissue [XREF_BIBR]."

reach
"In addition, USP12 knockdown increased apoptosis in HCC cell lines."

reach
"Besides, flow cytometry apoptosis Annexin V-PI staining assay indicated that USP12 deletion promoted apoptosis, and YAP overexpression was able to rescue this effect (Fig. 5I, J)."

reach
"Additionally, only the overexpression of USP12 promoted cell cycle progression (Fig. 3F, G) and inhibited apoptosis (Fig. 3H, I), whereas USP12 did not."

reach
"Depletion of USP12 decreased PC cell proliferation, increased apoptosis and caused G 1 arrest ( Burska et al., 2013 and McClurg et al., 2014 )."
WDR48 affects USP46
| 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 )."
USP12 affects PPM1B
1 | 11 1
USP12 deubiquitinates PPM1B.
| 6
USP12 deubiquitinates PPM1B. 6 / 6
| 6

reach
"Yang et al. found that USP12 and USP46 deubiquitinates and stabilizes PPM1B to regulate chemokine production in tumor cells ( Yang et al., 2021 )."

reach
"USP12 regulates chemokine production by deubiquitinating PPM1B."

reach
"The interaction between PPM1B and USP12 was then validated (Fig. 4c), raising the question of whether USP12 deubiquitinates PPM1B."

reach
"The ubiquitination experiments showed that ectopic expression of USP12 but not the C48S mutant decreased the levels of PPM1B polyubiquitination (Fig. 4d)."

reach
"We found that USP12 downregulation caused insufficient deubiquitination of PPM1B and thereby facilitated tumour growth by promoting the generation of the protumourigenic milieu."

reach
"For example, USP12 is described above as promoting NF-κB activation for NLRP3 inflammatory microsome production, but in NSCLC it inhibits NF-κB signaling activity and regulates chemokine secretion by deubiquitinating and stabilizing PPM1B."
USP12 ubiquitinates PPM1B.
| 3
USP12 leads to the ubiquitination of PPM1B. 3 / 3
| 3

reach
"The substrate of USP12, protein phosphatase magnesium-dependent 1B (PPM1B), acts as a phosphatase for IκB kinase β (IKKβ); thus, downregulation of USP12 can accelerate PPM1B ubiquitination and degradation, promoting NF-κB activation and influencing the immune microenvironment."

reach
"In Kras -driven lung cancer, USP12 suppression, triggered by AKT-mTOR signaling, leads to inadequate deubiquitination of PPM1B, resulting in NF-κB signaling hyperactivation and the creation of an immune-suppressive milieu."

reach
"USP12 downregulation in tumour cells accelerates PPM1B ubiquitination and degradation and therefore promotes NF-κB activity in orchestrating the TME."
USP12 binds PPM1B.
1 | 1 1
1 | 1 1

reach
"The interaction between PPM1B and USP12 was then validated (Fig. 4c), raising the question of whether USP12 deubiquitinates PPM1B."

sparser
"Thus, targeting the USP12-PPM1B cascade may perturb the TME and increase the efficacy of immune checkpoint blockade in certain cancers."

No evidence text available
USP12 increases the amount of PPM1B.
| 1
USP12 increases the amount of PPM1B. 1 / 1
| 1

reach
"As expected, USP12 knockdown decreased the levels of both PPM1B and IκB (Fig. 4e)."
AR affects USP12
3 | 5 5
AR binds USP12.
3 | 3 5
3 | 3 5

No evidence text available

sparser
"Although we were able to confirm the USP12- AR FL interaction we could not detect any interaction between USP12 and AR V7 (Figure xref )."

sparser
"To validate this result we overexpressed USP12 with AR FL, N-terminus of AR (AR ND) and AR N-terminus with DNA binding domain (AR ND-DNA BD) to localise the USP12-AR interaction."

sparser
"The requirement of the AR ligand binding domain to ensure an interaction between USP12 and AR is supported by our results in Figure xref showing that AR FL is stabilised following USP12 overexpression whereas the AR V7 proteins levels are unaffected (Figure xref )."

No evidence text available

reach
"To investigate if this was caused by the lack of interaction between AR and Usp12 in the absence of the specific serine residues, we overexpressed Usp12 alongside wild-type and mutant ARs followed by immunoprecipitation."

reach
"The requirement of the AR ligand binding domain to ensure an interaction between USP12 and AR is supported by our results in Figure XREF_FIG showing that AR FL is stabilised following USP12 overexpression whereas the AR V7 proteins levels are unaffected."

reach
"We have recently reported that Usp12, in complex with Uaf-1 and WDR20, can directly bind and deubiquitinate the AR resulting in increased receptor stability and transcriptional activity [XREF_BIBR]."

sparser
"To investigate if this was caused by the lack of interaction between AR and Usp12 in the absence of the specific serine residues, we overexpressed Usp12 alongside wild-type and mutant ARs followed by immunoprecipitation."

sparser
"Usp12 was capable of interacting with both AR S213A and AR S213A/S791A with comparable efficiency to wild-type confirming that these sites are not required for this interaction (Figure xref )."
AR activates USP12.
| 2
AR activates USP12. 2 / 2
| 2

reach
"Akt inhibition abrogated S213 phosphorylation of AR and decreased the ability of Usp12 to stabilise AR protein levels."

reach
"USP12 in the presence of its cofactors Uaf-1 and WDR20 deubiquitinates AR to enhance AR protein stability and transcriptional activity [71] USP12 in complex with Uaf-1 and WDR20 also abrogates phospho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 affects YAP1
| 11 1
USP12 deubiquitinates YAP1.
| 4
USP12 deubiquitinates YAP1. 4 / 4
| 4

reach
"Further ubiquitination experiments demonstrated that only the USP12 could deubiquitinate YAP proteins, while the mutant USP12 , lacking deubiquitinating enzyme activity, could not (Fig. 7E, F)."

reach
"The results showed that the deubiquitination of YAP by USP12 was observed in both nucleus and cytoplasm (Supplementary Fig. S3A)."

reach
"Besides, USP12 interacted with YAP protein, suppressing YAP poly-ubiquitination by K48-linked and preventing proteasome-mediated degradation in gastric cancer cells."

reach
"To further elucidate the mechanism by which USP12 deubiquitinates YAP, we investigated the specific site on the YAP protein targeted by USP12."
USP12 increases the amount of YAP1.
| 3
USP12 increases the amount of YAP1. 3 / 3
| 3

reach
"Furthermore, only USP12 modulated the expression of YAP target genes (Fig. 4G)."

reach
"Western blot analysis showed that the deletion of USP12 decreased levels of YAP protein in AGS and MKN74 cell lines (Fig. 4A)."

reach
"Western blotting results demonstrated that USP12 increased the protein level of YAP, whereas USP12 did not have the same effect (Fig. 4F)."
USP12 activates YAP1.
| 3
USP12 activates YAP1. 3 / 3
| 3

reach
"We then investigated the effect of USP12 overexpression on YAP protein half-life and found that USP12 overexpression increased YAP protein stability, whereas USP12 enzyme inactivation mutants USP12 did not (Fig. 6G, H)."

reach
"Taken together, these findings indicate that USP12 can activate HIPPO/YAP signaling, with this effect being dependent on its deubiquitinating enzyme activity."

reach
"Notably, USP12 depletion was found to inhibit gastric cancer progression via the Hippo/YAP axis, whereas USP12 overexpression exhibited the opposite effect, promoting gastric cancer growth and enhancing YAP activity."
USP12 binds YAP1.
| 1 1
| 1 1

sparser
"Moreover, USP12 interacts with the YAP protein to inhibit its degradation in cancer cells, stabilizing YAP by impeding YAP K48-linked polyubiquitination at the K315 site of YAP ( xref )."

reach
"Additionally, the Co-IP assay confirmed the interaction between USP12 and YAP (Fig. 6B, C)."
USP12 affects AKT
| 12
USP12 inhibits AKT.
| 5
USP12 inhibits AKT. 5 / 5
| 5

reach
"Future studies have to be directed to address this possibility.Gangula and Maddika earlier showed that USP12 was shown to suppress Akt-dependent cell survival signalling by stabilizing ser/thr phospha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Thus, these results suggest that WDR48 and USP12 negatively regulate Akt signaling and thereby induce apoptosis in conjunction with PHLPP1."

reach
"WDR48 and USP12 Negatively Regulate Akt Signaling and Promote Apoptosis."

reach
"Because PHLPP1 is a potent negative regulator of the PI3-kinase and Akt pathway, we hypothesized that WDR48 and USP12 might suppress Akt signaling by stabilizing PHLPP1."

reach
"As knockdown of WDR48 and USP12 increased Akt activation, we next tested whether WDR48 and USP12 could potentiate the suppression of Akt signaling by PHLPP1."
USP12 deubiquitinates AKT.
| 3
USP12 deubiquitinates AKT. 2 / 2
| 2

reach
"Knockdown of USP12 blocked prostate cancer proliferation, increased apoptosis and G1 arrest [ 15 ], and the mechanism of action was that USP12 could directly deubiquitinate and stabilize Akt phosphata[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 deubiquitinates AKT on leucine. 1 / 1
| 1

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 phosphorylates AKT.
| 2
USP12 leads to the phosphorylation of AKT. 2 / 2
| 2

reach
"Knockdown of Usp12, or its complex members Uaf-1 and WDR20, increased Akt phosphorylation without any change to the total Akt protein in PC cells."

reach
"Secondly, Usp12 deubiquitinates and stabilises PHLPP and PHLPPL proteins which enhances dephosphorylation and deactivation of Akt."
USP12 dephosphorylates AKT.
| 1
USP12 dephosphorylates AKT. 1 / 1
| 1

reach
"XREF_BIBR Notably, a recent study that screened a panel with 22 deubiquitinating enzymes in vitro showed that galeterone inhibits the enzymatic activity of USP12 and also binds directly to the USP12 and USP12 and UAF1 complexes, which dephosphorylate AKT."
USP12 activates AKT.
| 1
USP12 activates AKT. 1 / 1
| 1

reach
"On the other hand, USP12 can also stabilize AR proteins and enhance their transcriptional activity by stabilizing the AKT (protein kinase B) dephosphorylases (PHLPP and PHLPPL) (McClurg et al., 2014)."
PHLPP2 affects USP12
4 | 3 3
4 | 3 2

reach
"Here we report that Usp12, in complex with Uaf-1 and WDR20, interacts with PHLPP and PHLPPL in PC cells resulting in their deubiquitination and protein stabilisation."

No evidence text available

reach
"We demonstrated that Usp12, and two Usp12 interacting proteins, Uaf-1 and WDR20 [XREF_BIBR], [XREF_BIBR], form a complex with PHLPP and PHLPPL."

sparser
"The Usp12 complex interacts with PHLPP and PHLPPL."

sparser
"In agreement with the previous study, we found that both PHLPP (Figure xref ) and PHLPPL (Figure xref ) interacted with Usp12."

No evidence text available

No evidence text available

reach
"In agreement with the previous study, we found that both PHLPP and PHLPPL interacted with Usp12."

No evidence text available
| 1

sparser
"Both Usp12 and WDR20 alone were able to interact with both PHLPP (Figure xref ) and PHLPPL (Figure xref )."
USP12 affects Hypertrophy
| 10
USP12 activates Hypertrophy.
| 8
| 8

reach
"Lu et al. revealed that USP12 promoted Ang II-induced cardiomyocyte hypertrophy; METTL3 expression was induced by Ang II but was downregulated in USP12 knockdown neonatal rat cardiomyocytes (NRCMs)."

reach
"We found that USP12 promoted Ang II-induced cardiomyocyte hypertrophy, and USP12 deficiency attenuated cardiac hypertrophy in mice."

reach
"These results describing above confirmed that USP12 aggravates Ang II-induced cardiomyocyte hypertrophy via regulating METTL3.Next, we sought to figure out the molecular mechanism by which USP12 regul[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"According to a recent study, USP12 (ubiquitin-specific protease 12) via enhancing p300/MTLL3 axis promote myocardial hypertrophy [61], and our finding may indicate the possibility of m A methylation and ubiquitination cooperatively regulate heart growth."

reach
"Collectively, these findings indicated that USP12 was increased in Ang II-induced cardiac hypertrophy and may play a role in the pathogenesis of cardiac hypertrophy.To determine the role of USP12 in A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"As shown in Fig. 2 B–D, the expression levels of fetal genes and the size of cardiomyocyte were reduced in USP12-silenced NRCMs, indicating that USP12 inhibition could attenuate Ang II-induced cardiom[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Next, we evaluated the effect of USP12 knockout on cardiac hypertrophy, the results showed that USP12 deletion attenuated the phenotype of Ang II-induced cardiac hypertrophy ( Fig. 2 I and J)."

reach
"Our study demonstrated that USP12 promoted Ang II-induced cardiac hypertrophy via regulating METTL3 expression."
USP12 inhibits Hypertrophy.
| 2
| 2

reach
"Overexpression USP12 aggravates cardiac hypertrophy, whereas inhibition of USP12 ameliorates Ang II-induced myocardial hypertrophy [156]."

reach
"As shown in Fig. 3 F–H, upregulation of METTL3 exacerbated the Ang II-induced myocardial hypertrophy, more important, re-expression of METTL3 could reverse the decrease of cardiomyocyte size and hyper[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
UAF1 affects USP12
| 10
UAF1 activates USP12. 10 / 10
| 10

eidos
"With a mutation introduced to the BL1 residue F262 , USP12 could no longer be activated by UAF1 but retained full WDR20-stimulated activity ( Figures 6D and 6E ) ."

eidos
"Nevertheless , the free USP12 structure alone is insufficient to link these predicted changes to USP12 activation by UAF1 or WDR20 ."

eidos
"To delineate the mechanism by which UAF1 activates USP12 , we next determined the crystal structure of USP12 in a complex with full-length human UAF1 in the F222 space group at 3 ."

eidos
"This result clearly indicates that UAF1 and WDR20 allosterically activate USP12 through two distinct pathways ."

eidos
"To gain deeper mechanistic insights into USP12 activation by UAF1 and WDR20 , we first determined the steady-state kinetics of substrate hydrolysis by USP12 in different forms ."

eidos
"Activation of USP12 by UAF1 requires structural fine-tuning at the junction of the Ub globular domain and it tail through BL1 , whereas WDR20 acts independently of this site and directly affects the catalytic cleft ."

eidos
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20 Ubiquitin-specific proteases ( USPs ) constitute the largest family of deubiquitinating enzymes , whose catalytic competency is often modulated by their binding partners through unknown mechanisms ."

eidos
"First , our results rule out the possibility that UAF1 and WDR20 activate USP12 by enhancing its substrate affinity ."

eidos
"Based on our results , we propose a tenable model for USP12 activation by UAF1 and WDR20 ( Figure 7 ) ."

eidos
"UAF1 activates USP12 by binding to the tip of its Fingers domain and transmitting a long-range allosteric signal to BL1 ."
DMWD affects USP12
5 | 3 2
DMWD binds USP12.
5 | 1 2
5 | 1

No evidence text available

No evidence text available

No evidence text available

reach
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."

No evidence text available

No evidence text available
USP12 binds DMWD and WDR20. 1 / 1
| 1

sparser
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
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 USP12.
| 2
DMWD activates USP12. 2 / 2
| 2

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
"Finally, we show that both DMWD and WDR20 promote USP12 enzymatic activity, but they differentially modulate the subcellular localization of the DUB."
USP12 affects RRM2
3 | 6
USP12 binds RRM2.
3 | 2
3 | 2

reach
"Here we showed that ubiquitin-specific peptidase 12 (USP12) directly interacts with and deubiquitinates RRM2 in non-small cell lung cancer (NSCLC) cells."

No evidence text available

No evidence text available

reach
"Moreover, recent research has shown that USP12 directly interacts with and deubiquitinates RRM2 in NSCLC."

No evidence text available
USP12 deubiquitinates RRM2.
| 3
USP12 deubiquitinates RRM2. 3 / 3
| 3

reach
"Here we showed that ubiquitin-specific peptidase 12 (USP12) directly interacts with and deubiquitinates RRM2 in non-small cell lung cancer (NSCLC) cells."

reach
"Moreover, recent research has shown that USP12 directly interacts with and deubiquitinates RRM2 in NSCLC."

reach
"For example, USP12 could deubiquitinate RRM2 and promote non-small cell lung cancer progression [30]."
USP12 activates RRM2.
| 1
USP12 activates RRM2. 1 / 1
| 1

reach
"Furthermore, the deubiquitinase USP12 has been discovered to positively modulate the protein abundance of RRM2 through deubiquitination 34."
USP12 affects IFNB1
| 9
USP12 activates IFNB1.
| 6
USP12 activates IFNB1. 6 / 6
| 6

reach
"Furthermore, USP12 significantly enhanced the IFN-β promoter activity mediated by IFI16/STING but not by TLR9/MYD88 and DDX41/STING (Fig 4A)."

reach
"By contrast, USP12 enhanced IFN-β, NF-κB, and ISRE promoter activities in a dose-dependent manner after cotransfection with IFI16 (Fig 4B)."

reach
"Results show that USP12 deficiency significantly inhibited IFN-β, CXCL5, and IL-6 production in BMDMs and MEFs infected with a DNA virus, although not in BMDMs infected with an RNA virus (Figs 1A and S2A)."

reach
"The exogenous overexpression of USP12 in HEK293T cells promoted DNA-virus induced luciferase activities of IFN-β, ISRE, and NF-κB promoters (Fig 1C)."

reach
"Similarly, the knockdown of USP12 decreased IFN-β, CCL5, and IL-6 production in the DNA virus infected-groups but not in the RNA virus infected-group (Fig 2A)."

reach
"The overexpression of human USP12 promoted DNA virus-induced luciferase activities of IFN-β, ISRE, and NF-κB promoters."
USP12 increases the amount of IFNB1.
| 2
USP12 increases the amount of IFNB1. 2 / 2
| 2

reach
"By contrast, IFI6 overexpression in Usp12 BMDMs promoted the expression of IFN-β and IL-6 (Fig 7C) and phosphorylation of IRF3 and p65 (Fig 7D)."

reach
"In this study, we found that knockout or knockdown of USP12 impaired the HSV-1-induced expressions of IFN-beta, CCL-5, IL-6, and downstream interferon-stimulated genes (ISGs)."
USP12 decreases the amount of IFNB1.
| 1
USP12 decreases the amount of IFNB1. 1 / 1
| 1

reach
"Usp12 overexpression in Ifi16 BMDMs did not rescue the reduced expression of IFN-β and IL-6 caused by Ifi16 deficiency (Fig 7B)."
METTL3 affects USP12
| 6 3
METTL3 binds USP12.
| 1 3
| 1 3

sparser
"Co-immunoprecipitation (co-IP) result suggested that there was no interaction between USP12 and METTL3 under the stimulation of Ang II ( Supplementary Fig. 4A )."

sparser
"However, the result of co-IP assay showed that USP12 did not interact with METTL3, indicating that there was a transcriptional regulatory mechanism between USP12 and METTL3."

reach
"Thus, we detected whether there was an interaction between USP12 and METTL3."

sparser
"Thus, we detected whether there was an interaction between USP12 and METTL3."
METTL3 activates USP12.
| 4
METTL3 activates USP12. 4 / 4
| 4

reach
"This result suggested that METTL3 may mediate the pro-hypertrophic function of USP12."

reach
"METTL3 acted as a pathogenic factor and mediated the pro-hypertrophy effect of USP12 in Ang-II-induced myocardium remodeling [9]."

reach
"These data led us to investigate whether METTL3 mediated the pro-hypertrophic function of USP12."

reach
"Importantly, upregulation of METTL3 reversed the decrease of Ang II-induced myocardial hypertrophy in USP12-silenced NRCMs."
METTL3 inhibits USP12.
| 1
METTL3 inhibits USP12. 1 / 1
| 1

reach
"And, the RNA-seq data indicate that the expression of METTL3 was upregulated under the treatment of Ang II, while was reduced in USP12-silenced NRCMs ( Fig. 3 A)."
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 )."
| 1 5

reach
"Moreover, overexpressing USP12 in gastric cancer cell lines enhanced cell migration and invasion, while overexpression of USP12 did not (Fig. 3D, E)."

reach
"Therefore, the mechanism of action of USP12 on apoptosis and autophagy merits more investigation to develop novel insight into therapeutic strategies.Besides the above, USP12 has also been proven to mediate cancer invasion and metastasis."

reach
"Moreover, the transwell assay showed that overexpression of YAP partially restored the cell migration and invasion suppressed by USP12 deletion (Fig. 5E, F)."

reach
"Additionally, the transwell assay revealed that USP12 deletion decreased cell invasion and migration (Fig. 2D–G)."

eidos
"In the present study , we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic ( M ) - MDSCs , resulting in increased CD8 + T cell response and decelerated tumor growth ."

reach
"In the present study, we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic (M)-MDSCs, resulting in increased CD8 + T cell response and decelerated tumor growth."

reach
"A recent study suggested that USP12 enhances the infiltration and suppressive function of M-MDSCs concomitant with PD-L1 upregulation through the deubiquitination and stabilization of NF-κB p65 [26]."

reach
"The absence of USP12 reduces the infiltration of mononuclear (M)-MDSCs and impairs their suppressive function, leading to enhanced CD8 + T-cell responses and reduced tumor growth [60]."
USP12 affects Histone_H2B
| 8
USP12 deubiquitinates Histone_H2B. 8 / 8
| 8

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

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

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

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

reach
"Monoubiquitination of H2B can be restored by the inhibition of the deubiquitinases USP12, USP44 and USP7 [115]."

reach
"It was shown that USP12 deubiquitinates histones H2A and H2B both in vitro and in vivo [3] ."

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]"
USP12 affects DMWD
5 | 1 2
5 | 1

No evidence text available

No evidence text available

No evidence text available

reach
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."

No evidence text available

No evidence text available
USP12 binds DMWD and WDR20. 1 / 1
| 1

sparser
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
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."
EP300 affects USP12
2 | 4 2
EP300 binds USP12.
2 | 1 2
2 | 1 2

sparser
"Therefore, we observed whether there was interaction between the USP12 protein and p300 protein."

No evidence text available

No evidence text available

sparser
"Mechanically, USP12 bind to p300 protein and inhibited its degradation, thus promoting the transcription of METTL3."

reach
"Mechanically, USP12 bind to p300 protein and inhibited its degradation, thus promoting the transcription of METTL3."
EP300 activates USP12.
| 2
EP300 activates USP12. 2 / 2
| 2

reach
"In addition, we verified that p300 is the key for USP12-mediated enhancement of METTL3, as overexpression of p300 rescued the decrease of METTL3 expression in USP12-silenced NRCMs, while reducing p300[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Taken together, these data demonstrated that transcription factor p300 mediated the regulation of USP12 on METTL3.Finally, we wanted to explore how USP12 regulated p300."
EP300 inhibits USP12.
| 1
EP300 inhibits USP12. 1 / 1
| 1

reach
"Furthermore, we transfected p300 overexpression adenovirus into NRCMs to upregulate p300 expression and found that overexpression of p300 rescued the decrease of METTL3 expression and cardiomyocyte hy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 affects USP1
1 | 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 ]."
1 |

No evidence text available
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."
USP12 affects TGFB
| 7
USP12 activates TGFB. 7 / 7
| 7

reach
"The dauer larva-constitutive C. elegans phenotype caused by defective DAF-7 and TGF-beta signaling was enhanced and suppressed, respectively, by ubh-1 deletion and overexpression in the loss-of-function genetic backgrounds of daf7, daf-1 and TGF-betaRI, and daf4 and R-SMAD, but not of daf-8 and R-SMAD."

reach
"This suggested that UBH-1 may stimulate DAF-7 and TGF-beta signaling via DAF-8 and R-SMAD."

reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."

reach
"The dauer larva-constitutive C. elegans phenotype caused by defective DAF-7 and TGF-beta signaling was enhanced and suppressed, respectively, by ubh-1 deletion and overexpression in the loss-of-function genetic backgrounds of daf7, daf-1 and TGF-betaRI, and daf4 and R-SMAD, but not of daf-8 and R-SMAD."

reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."

reach
"This suggested that UBH-1 may stimulate DAF-7 and TGF-beta signaling via DAF-8 and R-SMAD."

reach
"The authors showed that UBH-1 in Caenorhabditis elegans and its human homolog UCHL1 promotes DAF-7/ TGF-β signalling, indicating that the mechanism of TGF-β signalling is conserved among animal species [67]."
| 5

reach
"It has been mentioned previously that USP12 silencing inhibits PC cell proliferation, induces cell cycle arrest, and promotes apoptosis [42]."

reach
"Furthermore, Usp12 silencing was shown to reduce proliferation of PC cells."

reach
"Depletion of USP12 decreased PC cell proliferation, increased apoptosis and caused G 1 arrest ( Burska et al., 2013 and McClurg et al., 2014 )."

reach
"As a result Usp12 promotes PC development with protein levels increased in PC patients compared to benign controls."

reach
"On the other hand, USP12 promoted prostate cancer (PC) cells proliferation by forming a complex with Uaf-1 and WDR20 and deubiquitinating AR, thereby increasing AR stability and transcriptional activity, whereas USP12 silencing led to a significant decrease in PC cell proliferation [42, 64]."
| 1

reach
"As a result, depleting Usp12 decreased PC cellular proliferation and increased cellular apoptosis suggesting it may be a potential target for CRPC therapy [XREF_BIBR]."
USP12 deubiquitinates Prostatic Neoplasms.
| 1
| 1

reach
"USP12 also deubiquitinates AR and MDM2, which in turn controls TP53 levels and exerts a regulatory effect on PC by controlling the TP53-MDM2-AR-AKT signaling pathway [68]."
USP12 affects Notch
| 7
USP12 inhibits Notch.
| 2
USP12 inhibits Notch. 2 / 2
| 2

reach
"CG7023 and USP12 was shown to negatively regulate Notch signaling in flies."

reach
"USP12 was also demonstrated to negatively regulate Notch signaling by influencing Notch trafficking to the lysosomes [ 17 ]."
USP12 deubiquitinates Notch.
| 2
USP12 deubiquitinates Notch. 2 / 2
| 2

reach
"At the biochemical level, USP12 with its activator UAF1 deubiquitinate the nonactivated form of Notch in cell culture and in vitro."

reach
"USP12 activates UAF1 at the biochemical level, causing the deubiquitination of Notch in cells and in vitro."
USP12 activates Notch.
| 2
USP12 activates Notch. 2 / 2
| 2

reach
"Specifically silencing USP12 impedes the transport of Notch to lysosomes, resulting in an increase in cell surface receptors and heightened Notch activity."

reach
"The Ubiquitin specific Protease 12 (USP12) is a negative regulator of Notch signaling as USP12 directly targets Notch and directs it to lysosomal degradation."
USP12 increases the amount of Notch.
| 1
USP12 increases the amount of Notch. 1 / 1
| 1

reach
"USP12 down-regulation leads to an increased level of Notch molecules at the cell surface."
USP1 affects USP12
1 | 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 ]."
1 |

No evidence text available
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."
HMGB1 affects USP12
4 | 1 2
4 | 1 2

reach
"Recently, it was reported that USP12, another USP family member, is highly expressed in multiple myeloma cells and binds to HMGB1 to deubiquitinate and stabilize HMGB1, resulting in the promotion of pro-survival autophagy in myeloma (Li et al. 2022)."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"In the context of autophagy, the study of multiple myeloma (MM) showed that USP12 could interact with the key autophagy mediator HMGB1 (high mobility group box-1) protein to deubiquitinate and stabilize it [ xref ]."

sparser
"This suggests that targeting the USP12-HMGB1 axis could have therapeutic potential in human myeloma [ 80 ] ( Fig. 2 A)."
USP12 affects cell cycle
| 2 4
USP12 activates cell cycle.
| 1 4
| 1 3

reach
"Additionally, only the overexpression of USP12 promoted cell cycle progression (Fig. 3F, G) and inhibited apoptosis (Fig. 3H, I), whereas USP12 did not."

reach
"Our data also indicated that over-expression of USP12 WT and its deubiquitinase enhanced mutants promoted cell cycle progression."

reach
"Flow cytometry analysis also showed that USP12 could induce cell cycle arrest at the G2/Mstage."

eidos
"In addition , USP12 promotes cell survival , proliferation , tumorigenesis , and cell cycle progression by upregulating BMI-1 , c-Myc , and cyclin D2 [ 24,25,26,27 ] ."
USP12-L153S activates cell cycle. 1 / 1
| 1

reach
"We report that USP12 L153S mutation is more powerful than the wild-type and R237C mutant to promote cell cycle progression and up-regulate the transcription of BMI-1, c-Myc and cyclin D2.The following[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 inhibits cell cycle.
| 1
| 1

eidos
"Flow cytometry analysis also showed that USP12 could induce cell cycle arrest at the G2 / M stage ."
USP12 affects TMPRSS11D
| 6
| 6

sparser
"In this study, we demonstrated that USP12 can bind with the HAT domain of CBP in vivo and in vitro ."

sparser
"Taken together, these findings suggest that USP12 binds to the HAT domain of CBP and blocks CBP’s acetyltransferase activity in cells."

sparser
"Interestingly, USP12 can interact with the HAT domain of CBP."

sparser
"The aforementioned results demonstrated that USP12 binds to the HAT domain of CBP and blocks CBP’s acetylation action."

sparser
"Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP’s acetyltransferase activity."

sparser
"In vitro binding assay further demonstrated that USP12 binds with the HAT domain of CBP ( xref )."
USP12 affects TCR
| 6
USP12 activates TCR.
| 4
USP12 activates TCR. 4 / 4
| 4

reach
"For instance, CYLD, USP8, USP15, USP18, USP34 and A20 negatively regulate TCR signaling, whereas USP9X, USP12, USP22, USP2a and Otud7b positively modulate TCR signaling."

reach
"After stimulating the TCR with an anti-CD3 antibody, phosphorylation of the USP12 cytoplasmic pool could be induced, allowing USP12 to translocate from the nucleus to the cytoplasm and acted directly on the substrate proteins LAT and Trat1 to stabilize the TCR complex on the T cell surface during signaling."

reach
"It has been also shown that USP12 deubiquitylated and prevented lysosomal degradation of T-cell receptor complex (TCR) to sustain TCR mediated signaling [ 20 ]."

reach
"In contrast, USP12 has been found to stabilize the TCR complex and promote TCR signaling through deubiquitylating TCR adaptor proteins LAT and Trat1 in primary mouse T lymphocytes."
USP12 deubiquitinates TCR.
| 2
USP12 deubiquitinates TCR. 2 / 2
| 2

reach
"Recently, USP12 was shown to stabilize the TCR complex at the cell surface by deubiquitinating TCR adaptor proteins LAT and Trat1."

reach
"Similarly, the ubiquitin specific peptidase 12 (USP12) can deubiquitinate LAT at the proximal TCR (Figure 2), to protect it from ubiquitin-dependent lysosomal degradation [146]."
| PMC
USP12 affects ITGB1
| 6
USP12 increases the amount of ITGB1.
| 4
USP12 increases the amount of ITGB1. 4 / 4
| 4

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."

reach
"Re-expression of USP12 in USP12/46-dKO or SNX17 in SNX17-KO fully restored the surface levels of Itgb1 (Fig. 3D)."

reach
"Co-expression of USP12 and SNX17 fully restored the Itgb1 levels in tKO fibroblasts, whereas separate expression of USP12 or SNX17 in tKO fibroblasts failed to normalize Itgb1 surface levels (Fig. 3D)."

reach
"Expression of USP12 in USP12/46-dKO fibroblasts rescued Itgb1 surface levels, whereas expression of USP12 or USP12 only partially rescued Itgb1 surface levels and expression of USP12 did not increase Itgb1 levels beyond the levels of USP12/46-dKO fibroblasts expressing EGFP-only (Figs."
USP12 inhibits ITGB1.
| 1
USP12 inhibits ITGB1. 1 / 1
| 1

reach
"Consistently, the loss of the two DUBs, USP12, and USP46, which compensate each other, or of either WDR20 or WDR48, which facilitates the DUB activity, decreases the protein stability of Itgb1."
USP12 deubiquitinates ITGB1.
| 1
USP12 leads to the deubiquitination of ITGB1. 1 / 1
| 1

reach
"Whereas USP12 -WDRs reduced Itgb1 ubiquitination, the catalytically inactive USP12 -WDRs did not."
USP12 affects Chemokine
| 6
USP12 decreases the amount of Chemokine.
| 3
USP12 decreases the amount of Chemokine. 3 / 3
| 3

reach
"The literature indicates that USP12 has been shown to diminish T-cell activation by facilitating the expression of specific chemokines."

reach
"In terms of NSCLC, USP12 was decreased upon the activation of AKT-mTOR signaling, and USP12 could reduce the levels of several chemokines, including CXCL8, CXCL1, CCL2, and CCL5, which were relevant to immune cell recruitment."

reach
"Given that USP12 negatively regulated protumourigenic chemokine expression and exerted a tumour-suppressive effect in immune-competent mice but not in immune-deficient mice, it seems intuitive to speculate that USP12 downregulation in tumours may help establish a favourable microenvironment for tumour growth."
USP12 activates Chemokine.
| 3
| 3

reach
"This study demonstrated that AKT-mTOR hyperactivation resulted in USP12 downregulation, which in turn increased the production of protumourigenic chemokine in NSCLC, indicating that USP12 is a regulatory node in oncogenic mutation-driven TME development.The tumour suppressive function conveyed by USP12 is virtually related to the control of protumourigenic chemokine expression."

reach
"Of note, the altered production of the chemokines caused by USP12 downregulation in tumour cells may also regulate T cell infiltration and function."

reach
"Given the relevance of the USP12-mediated chemokine, such as CXCL8, CXCL1 and CCL2, in tumour development and progression, we examined the mechanism underlying the USP12-mediated regulation."
TMPRSS11D affects USP12
| 6
| 6

sparser
"In this study, we demonstrated that USP12 can bind with the HAT domain of CBP in vivo and in vitro ."

sparser
"Taken together, these findings suggest that USP12 binds to the HAT domain of CBP and blocks CBP’s acetyltransferase activity in cells."

sparser
"Interestingly, USP12 can interact with the HAT domain of CBP."

sparser
"The aforementioned results demonstrated that USP12 binds to the HAT domain of CBP and blocks CBP’s acetylation action."

sparser
"Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP’s acetyltransferase activity."

sparser
"In vitro binding assay further demonstrated that USP12 binds with the HAT domain of CBP ( xref )."
USP46 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."

reach
"USP12 targeted IFI16 to enhance antiviral response."

reach
"USP12 sustained cellular p-STAT1 levels and promoted IFN signaling and antiviral response [ 18 ]."

reach
"However, it is unclear whether USP12 regulates nucleic acid sensors to modulate antiviral immune responses.In this study, we demonstrated that during DNA virus infection, USP12 positively regulates the IFI16-STING-mediated antiviral response through its deubiquitinase activity."

reach
"Overall, these experiments suggested that USP12 targets IFI16 to enhance antiviral response."

reach
"Moreover, our study has shown that the USP12-associated deubiquitination of IFI16 promoted an antiviral response."
USP12 affects daf-7
| 5
USP12 activates daf-7. 5 / 5
| 5

reach
"This suggested that UBH-1 may stimulate DAF-7 and TGF-beta signaling via DAF-8 and R-SMAD."

reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."

reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."

reach
"This suggested that UBH-1 may stimulate DAF-7 and TGF-beta signaling via DAF-8 and R-SMAD."

reach
"The authors showed that UBH-1 in Caenorhabditis elegans and its human homolog UCHL1 promotes DAF-7/ TGF-β signalling, indicating that the mechanism of TGF-β signalling is conserved among animal species [67]."
USP12 affects Neoplasms
| 5
USP12 activates Neoplasms.
| 4
| 4

reach
"Furthermore, depletion of USP12 effectively inhibited gastric cancer tumor growth in vivo in a xenograft model, and overexpression of YAP rescued this effect (Fig. 5K–M)."

reach
"The absence of USP12 reduces the infiltration of mononuclear (M)-MDSCs and impairs their suppressive function, leading to enhanced CD8 + T-cell responses and reduced tumor growth [60]."

reach
"For example, AKT-mTOR signaling in KRAS G12D NSCLC generates a tumor-promoting secretome and tumor-associated macrophage (TAM)-infiltration by downregulating the deubiquitinase, USP12 [ 20 ]."

reach
"Similar tumor-inducing effects of USP12 were observed in C33A cells and PC cells ( Burska et al., 2013, Lehoux et al., 2014 and McClurg et al., 2014 )."
USP12 inhibits Neoplasms.
| 1
| 1

reach
"Overexpression of USP12 inhibits tumor growth and alters TME components, while CXCL1 and CCL2 can mitigate this effect."
USP12 affects MDK
2 | 2 1
USP12 binds MDK.
2 | 1
2 | 1

sparser
"Thus, the USP12-MDK axis may be a potential target for breast cancer metastasis treatment [ xref ]."

No evidence text available

No evidence text available
USP12 deubiquitinates MDK.
| 2
USP12 deubiquitinates MDK. 2 / 2
| 2

reach
"Collectively, our study identified that USP12 is responsible for deubiquitinating and stabilizing MDK and leads to metastasis by promoting angiogenesis."

reach
"Indeed, a recent study reported that USP12 deubiquitinates and stabilizes MDK and this stabilization promotes breast cancer angiogenesis [42]."
USP12 affects LAT
1 | 4
USP12 deubiquitinates LAT.
| 4
USP12 deubiquitinates LAT. 4 / 4
| 4

reach
"Similarly, the ubiquitin specific peptidase 12 (USP12) can deubiquitinate LAT at the proximal TCR (Figure 2), to protect it from ubiquitin-dependent lysosomal degradation [146]."
| PMC

reach
"Mechanistically, USP12 deubiquitinates LAT and Trat1, and inhibits lysosomal degradation of LAT and Trat1 to maintain the proximal TCR complex for the duration of signaling, which is the first time fo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Further experiments indicated that USP12 deubiquitinates LAT and TRAT1 to prevent their monoubiquitination and lysosomal degradation, leading to the stabilization of the TCR complex at the cell surfac[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Recently, USP12 was shown to stabilize the TCR complex at the cell surface by deubiquitinating TCR adaptor proteins LAT and Trat1."
USP12 binds LAT.
1 |
1 |

No evidence text available
USP12 affects Interferon
| 5
USP12 activates Interferon.
| 4
| 4

reach
"USP12 sustained cellular p-STAT1 levels and promoted IFN signaling and antiviral response [ 18 ]."

reach
"Notably, USP12 positively regulates interferon antiviral signaling independent of its deubiquitinase activity."

reach
"Additionally, USP12 positively regulates IFN antiviral signaling independently of its deubiquitinase activity."

reach
"Interestingly, USP12 positively regulates interferon (IFN) antiviral signaling independently of its deubiquitinase activity."
USP12 increases the amount of Interferon.
| 1
USP12 increases the amount of Interferon. 1 / 1
| 1

reach
"In addition, USP12 knockdown decreased the mRNA levels of interferon-stimulated gene 15 ( ISG15 ), ISG54 and interferon-induced transmembrane protein 1 ( IFITM1 ) induced by IFNα, while USP12 overexpr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 affects IL6
| 5
USP12 decreases the amount of IL6.
| 2
USP12 decreases the amount of IL6. 2 / 2
| 2

reach
"Usp12 overexpression in Ifi16 BMDMs did not rescue the reduced expression of IFN-β and IL-6 caused by Ifi16 deficiency (Fig 7B)."

reach
"In RAW 264.7 macrophages, the ablation of USP12 inhibited the induction of LPS-induced iNOS and IL-6 expression but failed to alter IFN-β synthesis [ 19 ]."
USP12 phosphorylates IL6.
| 1
USP12 leads to the phosphorylation of IL6. 1 / 1
| 1

reach
"In addition, the knockdown of USP12 inhibited LPS-induced IL-6 synthesis and phosphorylation of ERK1/2 and p38-MAPKs but did not attenuate IFN-β production."
USP12 increases the amount of IL6.
| 1
USP12 increases the amount of IL6. 1 / 1
| 1

reach
"By contrast, IFI6 overexpression in Usp12 BMDMs promoted the expression of IFN-β and IL-6 (Fig 7C) and phosphorylation of IRF3 and p65 (Fig 7D)."
USP12 activates IL6.
| 1
USP12 activates IL6. 1 / 1
| 1

reach
"Knockdown of USP12 impaired the activation of the IFI16-STING-IRF3/NF-κB pathway triggered by DNA viruses and the expression of downstream genes, including IL6."
USP1 affects USP46
| 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."
RRM2 affects USP12
3 | 2
3 | 2

reach
"Here we showed that ubiquitin-specific peptidase 12 (USP12) directly interacts with and deubiquitinates RRM2 in non-small cell lung cancer (NSCLC) cells."

No evidence text available

No evidence text available

reach
"Moreover, recent research has shown that USP12 directly interacts with and deubiquitinates RRM2 in NSCLC."

No evidence text available

reach
"Fig. S2 Depletion of USP12 induced cell cycle arrest in HeLa cells."

reach
"Contrarily, a different study shows USP12 suppresses Akt-dependent cell growth of tumor cells by stabilizing tumor suppressor PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) [ 13 ]."

reach
"Besides, USP12 could induce HCC cell cycle arrest at the G2/M phase via the cell cycle protein-dependent kinase 1/cyclinB1 axis."

reach
"It has been mentioned previously that USP12 silencing inhibits PC cell proliferation, induces cell cycle arrest, and promotes apoptosis [42]."
| 4
USP12 inhibits ossification.
| 2
| 2

reach
"Overall, these findings highlight the primary involvement of the PERK/eIF2α/ATF4 signaling axis in USP12 depletion-mediated osteogenesis in hPDLCs.Deubiquitinases (DUBs) play a crucial role in bone me[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"USP12 depletion increased the osteogenesis of hPDLSCs under CTS."
USP12 activates ossification.
| 2
| 2

reach
"To investigate the mechanism underlying USP12 depletion-mediated osteogenesis, we employed specific inhibitors targeting the three UPR signaling branches, including PERK inhibitor (GSK2606414, 5 μM), [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"All these results suggested that USP12 KD enhanced the osteoblastic differentiation potential of hPDLCs under CTS.To unravel the intricate mechanisms through which USP12 modulates osteogenesis in hPDL[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 affects mHTT
| 4
USP12 inhibits mHTT.
| 2
USP12 inhibits mHTT. 2 / 2
| 2

reach
"USP12 may promote the degradation of mHTT by delivering mHTT to the autophagosomes (Aron et al., 2018)."

reach
"Catalytically inactive Usp12 suppresses mHTT toxicity."
USP12 binds mHTT.
| 2
USP12 binds mHTT. 2 / 2
| 2

reach
"Using the available association data for Usp12 and mHTT interactions, we mapped a protein protein interaction network between Usp12 and mHTT, and identified the autophagy receptor Optineurin (Optn) as a potential link."

reach
"The conserved association between USP12 and mHTT is worthy of further investigation aimed at revealing the specific mechanism [151]."

reach
"USP12 promoted LPS stimulated macrophage inflammatory responses via inhibition of IκBα [ 19 ]."

reach
"Most of the deubiquitinases, including A20 and CYLD, can inhibit NF-kappaB activation [XREF_BIBR], while USP12 positively regulates the LPS signal [XREF_BIBR]."

reach
"In addition, USP12, as a key mediator, promoted LPS stimulated macrophage inflammatory responses via inhibition of IκBα [ 19 ]."

reach
"USP12 also promotes LPS-induced signaling in macrophages through the dephosphorylation of IκBα [49]."
| 4
USP12 activates angiogenesis.
| 3
| 3

reach
"One study demonstrated that USP12 induced angiogenesis and metastasis by dehydrogenating and stabilizing the MDK protein (Figure 3) (103)."

reach
"Downregulation of USP12 also promotes NSCLC angiogenesis and upregulates PD-1 thus inducing resistance to anti-PD-L1 therapy [66]."

reach
"USP12 promotes breast cancer angiogenesis by maintaining midkine stability."
USP12 inhibits angiogenesis.
| 1
| 1

reach
"Overexpression of MDK rescued the loss of angiogenesis ability mediated by knockdown of USP12 in breast cancer cells in vitro and in vivo."
USP12 affects UL138
1 1 | 2
1 1 |

No evidence text available

No evidence text available
| 2

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pY701-STAT1."

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pSTAT1."
USP12 affects TRAT1
1 | 3
USP12 deubiquitinates TRAT1.
| 3
USP12 deubiquitinates TRAT1. 3 / 3
| 3

reach
"Recently, USP12 was shown to stabilize the TCR complex at the cell surface by deubiquitinating TCR adaptor proteins LAT and Trat1."

reach
"Mechanistically, USP12 deubiquitinates LAT and Trat1, and inhibits lysosomal degradation of LAT and Trat1 to maintain the proximal TCR complex for the duration of signaling, which is the first time fo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Further experiments indicated that USP12 deubiquitinates LAT and TRAT1 to prevent their monoubiquitination and lysosomal degradation, leading to the stabilization of the TCR complex at the cell surfac[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 binds TRAT1.
1 |
1 |

No evidence text available
USP12 affects TP53
| 3 1
USP12 increases the amount of TP53.
| 1
USP12 increases the amount of TP53. 1 / 1
| 1

reach
"Mechanistically, USP12 can promote the development of PCa by stabilizing MDM2 protein levels and reducing p53 levels (McClurg et al., 2018b)."
USP12 deubiquitinates TP53.
| 1
USP12 deubiquitinates TP53. 1 / 1
| 1

reach
"USP12 also deubiquitinates AR and MDM2, which in turn controls TP53 levels and exerts a regulatory effect on PC by controlling the TP53-MDM2-AR-AKT signaling pathway [68]."
USP12 decreases the amount of TP53.
| 1
USP12 decreases the amount of TP53. 1 / 1
| 1

reach
"Mechanistically, USP12 can promote the development of PCa by stabilizing MDM2 protein levels and reducing p53 levels (McClurg et al., 2018b)."
USP12 binds TP53.
| 1
| 1

sparser
"However, whether USP12 is associated with P53 in breast cancer remains to be further investigated."
USP12 affects SQSTM1
| 1 3
| 1 2

reach
"An interaction between Usp12 or Usp12-C48S and p62 was also confirmed by co-immunoprecipitation."

sparser
"An interaction between Usp12 or Usp12-C48S and p62 was also confirmed by co-immunoprecipitation (Fig.  xref )."

sparser
"The use of super resolution microscopy and immunoprecipitation assay showed significant colocalization of USP12-p62 and USP12-mHTT-Optineurin (another autophagy receptor)."
| 1

sparser
"We have found an intriguing interaction of Usp12 with p62 and Optn, two key receptors necessary for the selective-autophagic clearance of misfolded proteins, mitochondria, and protein aggregates."
USP12 affects NFKBIA
| 3 1
USP12 dephosphorylates NFKBIA.
| 1 1
USP12 dephosphorylates NFKBIA. 2 / 2
| 1 1

sparser
"Mechanistic analysis demonstrates that USP12 dephosphorylates IκBα, which is a well-characterized inhibitor of NF-κB nuclear translocation, inducing proinflammatory responses in macrophages."

reach
"Mechanistic analysis demonstrates that USP12 dephosphorylates IkappaBalpha, which is a well characterized inhibitor of NF-kappaB nuclear translocation, inducing proinflammatory responses in macrophages."
USP12 increases the amount of NFKBIA.
| 1
USP12 increases the amount of NFKBIA. 1 / 1
| 1

reach
"Knockdown of USP12 inhibited the NF-κB pathway by reducing the phosphorylation level of IkBa (degraded form), which was a kind of inhibitor of NF-κB nuclear translocation in LPS-induced macrophages, and an increased number of dephosphorylated IkBa was then translocated to the nucleus to inhibit the NF-κB pathway."
USP12 decreases the amount of NFKBIA.
| 1
USP12 decreases the amount of NFKBIA. 1 / 1
| 1

reach
"Moreover, the knockdown of USP12 increased the total protein level of IkBa in macrophages."
USP12 affects MAP1LC3
| 4
USP12 inhibits MAP1LC3.
| 2
| 2

reach
"Usp12 and Usp12-C48S overexpression significantly decreased the mean half-life of LC3, but did not affect the half-life of the control protein Dendra2."

reach
"Conversely, Usp12 knockdown increased the mean half-life of LC3, while also significantly right shifting the distribution of LC3 half-lives in individual neurons."
USP12 activates MAP1LC3.
| 2
Mutated USP12 activates MAP1LC3. 2 / 2
| 2

reach
"Moreover, there has no difference in the efficiency of USP12 and non-catalytic mutant of USP12 in stimulating the clearance of LC3, which is an autophagy protein that incorporates into autophagosomes, and selectivity degraded via autophagy."

reach
"Since a non catalytic mutant of Usp12, Usp12-C48S, stimulated LC3 clearance as efficiently as Usp12, we additionally conclude that this function of Usp12 is independent of its deubiquitinating activity."
USP12 affects CP
| 4
| 4

sparser
"As shown in Fig. 4 B, the anti-GFP Ab-immunoprecipitated protein complexes containing RGNNV CP were recognized by the anti-HA Ab, indicating that Ec USP12 could interact with RGNNV CP."

sparser
"In our study, during RGNNV infection, Ec USP12 was almost colocalized with CP, and the interaction between Ec USP12 and CP was further confirmed by Co-IP."

sparser
"Thus, it was speculated that the interaction between Ec USP12 and CP induced the changes of its localization during RGNNV infection."

sparser
"Furthermore, Ec USP12 could interact with viral CP in vitro ."
UL138 affects USP12
1 1 | 2
1 1 |

No evidence text available

No evidence text available
| 2

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pY701-STAT1."

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pSTAT1."
SQSTM1 affects USP12
| 1 3
| 1 2

reach
"An interaction between Usp12 or Usp12-C48S and p62 was also confirmed by co-immunoprecipitation."

sparser
"An interaction between Usp12 or Usp12-C48S and p62 was also confirmed by co-immunoprecipitation (Fig.  xref )."

sparser
"The use of super resolution microscopy and immunoprecipitation assay showed significant colocalization of USP12-p62 and USP12-mHTT-Optineurin (another autophagy receptor)."
| 1

sparser
"We have found an intriguing interaction of Usp12 with p62 and Optn, two key receptors necessary for the selective-autophagic clearance of misfolded proteins, mitochondria, and protein aggregates."
CP affects USP12
| 4
| 4

sparser
"As shown in Fig. 4 B, the anti-GFP Ab-immunoprecipitated protein complexes containing RGNNV CP were recognized by the anti-HA Ab, indicating that Ec USP12 could interact with RGNNV CP."

sparser
"In our study, during RGNNV infection, Ec USP12 was almost colocalized with CP, and the interaction between Ec USP12 and CP was further confirmed by Co-IP."

sparser
"Thus, it was speculated that the interaction between Ec USP12 and CP induced the changes of its localization during RGNNV infection."

sparser
"Furthermore, Ec USP12 could interact with viral CP in vitro ."
3 |
Valproic acid decreases the amount of USP12.
2 |
Valproic acid decreases the amount of USP12. 2 / 2
2 |

No evidence text available

No evidence text available
Valproic acid methylates USP12.
1 |
1 |

No evidence text available
WDR48 affects USP1
| 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 ]."
WDR20 affects USP46
| 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 )."
VSX2 affects USP12
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
VSX1 affects USP12
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP46 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 )."
USP12 affects cell growth
| 1 2
USP12 activates cell growth.
| 1 1
| 1 1

eidos
"Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy ."

reach
"Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy."
USP12 inhibits cell growth.
| 1
| 1

reach
"Contrarily, a different study shows USP12 suppresses Akt-dependent cell growth of tumor cells by stabilizing tumor suppressor PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) [ 13 ]."
USP12 affects VSX2
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP12 affects VSX1
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP12 affects Ubiquitin
| 2 1
USP12 inhibits Ubiquitin.
| 2
| 2

reach
"Elevated USP12 interacted with FOXO3, preventing its ubiquitin-mediated degradation, which enhanced FOXO3 binding to the PUMA promoter, leading to upregulation of PUMA."

reach
"Also, USP12 co-localizes with AR in the cytoplasm and promotes AR transcriptional activity by confronting the ubiquitin dependent degradation of AR [XREF_BIBR]."
USP12 binds Ubiquitin.
| 1

sparser
"Interestingly, it has been shown that USP12-Ub and UAF1 have two possible binding sites: The Finger domain and the back of the ubiquitin-binding cleft [ xref ]."
USP12 affects TEAD
| 3
USP12 activates TEAD.
| 2
USP12 activates TEAD. 2 / 2
| 2

reach
"According to the luciferase reporter assay in AGS and MKN74 cells, USP12 deletion inhibits TEAD response elements activity (Fig. 4D, E)."

reach
"Moreover, USP12 was found to enhance the transcriptional activity of TEAD, whereas USP12 did not demonstrate similar effects (Fig. 4H)."
USP12 inhibits TEAD.
| 1
USP12 inhibits TEAD. 1 / 1
| 1

reach
"Furthermore, qRT-PCR and luciferase assays indicated that YAP overexpression was able to reverse the down-regulation of Hippo target genes (Fig. 5B) and the decrease in TEAD transcriptional activity caused by USP12 deletion (Fig. 5C)."
USP12 affects RELA
| 3
USP12 phosphorylates RELA.
| 2
USP12 leads to the phosphorylation of RELA. 2 / 2
| 2

reach
"After STING activation, TBK1 is recruited and activated to induce the activation of downstream IRF3 and NF-κB. Further evaluations showed that USP12 deficiency decreased the phosphorylation of p65 and IRF3 induced by HSV-1 (S7A Fig) but not by VSV (S7B Fig)."

reach
"By contrast, IFI6 overexpression in Usp12 BMDMs promoted the expression of IFN-β and IL-6 (Fig 7C) and phosphorylation of IRF3 and p65 (Fig 7D)."
USP12 deubiquitinates RELA.
| 1
USP12 deubiquitinates RELA. 1 / 1
| 1

reach
"Furthermore, USP12 deficiency inhibited the suppressor function of M-MDSCs by downregulating the negative regulatory molecules iNOS and PD-L1, through deubiquitinating and stabilizing p65."
USP12 affects OPTN
| 1 2
| 1 1

reach
"Co-immunoprecipitation confirmed an interaction between Usp12 or Usp12-C48S and Optn."

sparser
"Co-immunoprecipitation confirmed an interaction between Usp12 or Usp12-C48S and Optn (Fig.  xref )."
| 1

sparser
"We have found an intriguing interaction of Usp12 with p62 and Optn, two key receptors necessary for the selective-autophagic clearance of misfolded proteins, mitochondria, and protein aggregates."

reach
"Therefore, the mechanism of action of USP12 on apoptosis and autophagy merits more investigation to develop novel insight into therapeutic strategies.Besides the above, USP12 has also been proven to mediate cancer invasion and metastasis."

reach
"Human umbilical vein endothelial cell (HUVEC) migration and angiogenesis assays demonstrated that overexpression of USP12 could promote breast metastasis, and USP12 depletion undermined the formation of lung metastatic nodules [73]."

reach
"Knockdown of USP12 decreased the lung metastasis ability of 4T1 cells, while USP12 overexpression increased the lung metastasis ability of these cells in vivo."
USP12 affects NOS2
| 3
USP12 decreases the amount of NOS2. 3 / 3
| 3

reach
"USP12 deficiency promoted the expression of inducible nitric oxide synthase (iNOS) in MDSCs by inhibiting the p65-NF-κB signaling pathway, and MDSCs with high iNOS expression inhibit T-cell function, resulting in poorer tumor response to chemotherapy [86]."

reach
"Consistent with this possibility, over-expression of USP12 robustly reduced both LPS and IFNγ-induced iNOS protein levels (data not shown) which is thematically consistent with the effects of PHLPP on[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In RAW 264.7 macrophages, the ablation of USP12 inhibited the induction of LPS-induced iNOS and IL-6 expression but failed to alter IFN-β synthesis [ 19 ]."
USP12 affects MYC
| 3
| 2

sparser
"Western blotting performed using varying concentration of Myc-USP12 to evaluate the dose-dependent expression levels of Bax revealed no increase in the protein levels of Bax when exposed to dose-dependent concentrations of Myc-USP12 ( xref C,D)."

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]"
MYC binds KLF5, USP12, and PARD6B. 1 / 1
| 1

sparser
"These super-enhancer amplifications are associated with over-expression of the MYC oncogene as well as the KLF5 , USP12 and PARD6B genes."
USP12 affects MMP14
2 | 1
USP12 binds MMP14.
2 |
2 |

No evidence text available

No evidence text available
USP12 deubiquitinates MMP14.
| 1
USP12 deubiquitinates MMP14. 1 / 1
| 1

reach
"It was demonstrated that circ-ADRM1 recruited USP12 to promote the deubiquitination of MMP14 protein, thus enhancing the stability of MMP14 protein."
USP12 affects MDM2
1 1 | 1
USP12 deubiquitinates MDM2.
1 | 1
USP12 deubiquitinates MDM2. 2 / 2
1 | 1

reach
"We find that USP12 deubiquitinates MDM2 and AR, which in turn controls the levels of the TP53 tumour suppressor and AR oncogene in prostate cancer."

"We find that <span class="match term0">USP12</span> deubiquitinates <span class="match term1">MDM2</span> and AR, which in turn controls the levels of the TP53 tumour suppressor and AR oncogene in prostate cancer."
USP12 binds MDM2.
1 |
1 |

No evidence text available
USP12 affects ITCH
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP12 affects ISG
| 3
USP12 increases the amount of ISG. 3 / 3
| 3

reach
"A previous study has demonstrated that USP12 regulates the IFN/JAK-mediated ISG expression by inhibiting the CBP acetyltransferase activity."

reach
"However, IFI16 deficiency did not rescue the reduced ISG expression caused by USP12 deficiency (S10A Fig)."

reach
"Moreover, USP12 overexpression upregulated ISG (ISG15, MX1, and IFIT1) expression (S5C and S5D Fig) and significantly inhibited HSV-1 and VSV replication, as indicated by the RNA levels (S5E Fig) and viral titers (S5F Fig)."
USP12 affects Histone
| 3
USP12 deubiquitinates Histone-H2A. 3 / 3
| 3

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
"It was shown that USP12 deubiquitinates histones H2A and H2B both in vitro and in vivo [3] ."

reach
"USP12 and USP46 can deubiquitinate histones H2A and H2B, thereby playing a critical role in Xenopus development [91] ."
USP12 affects FH
| 3
| 3

sparser
"Flag-HA tagged USP12 (FH-USP12) can bind with HA-CBP ( xref ) or endogenous CBP ( xref )."

sparser
"The results showed that CBP induced Flag-STAT1 acetylation in vitro , which was gradually inhibited by increasing amounts of FH-USP12 ( xref ), suggesting that USP12 blocks the acetylation effect of CBP on STAT1."

sparser
"We further found that FH-USP12 can interact with HA-p300 in cells ( xref )."
| 1 2
USP12 activates Cell Survival.
| 1 1
| 1 1

eidos
"In addition , USP12 promotes cell survival , proliferation , tumorigenesis , and cell cycle progression by upregulating BMI-1 , c-Myc , and cyclin D2 [ 24,25,26,27 ] ."

reach
"Overexpression of USP12 increases cell survival after mHTT expression in primary neurons and HD patient cells and decreases the mHTT-induced phenotype in Drosophila."
USP12 inhibits Cell Survival.
| 1

reach
"However, USP12 has also been shown to inhibit AKT-dependent cell survival by stabilizing the pro-apoptotic phosphatases PHLPP1 and/or PHLPPL ."

reach
"USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2."

eidos
"USP12 promotes nonsmall cell lung cancer progression through deubiquitinating and stabilizing RRM2 ."

reach
"Here, we show that the deubiquitinase USP12 is commonly downregulated in the Kras G12D -driven mouse lung tumour and human non-small cell lung cancer owing to the activation of AKT-mTOR signalling."
USP12 affects BCL10
| 3
USP12 activates BCL10.
| 2
USP12 activates BCL10. 2 / 2
| 2

reach
"In addition, USP12 activates CD4 + T cell proliferation by stabilizing BCL10 and targeting the NF-κB signaling pathway."

reach
"USP12 primarily modulates the activation and phenotype of T cells by regulating B-cell lymphoma 10 (BCL10)."
USP12 deubiquitinates BCL10.
| 1
USP12 deubiquitinates BCL10. 1 / 1
| 1

reach
"Specifically, USP12 deubiquitinates BCL10, maintaining its stability and activating the NF-κB pathway to stimulate CD4 + T-cell responses."
| 3
| 3

reach
"Lu et al. revealed that USP12 promoted Ang II-induced cardiomyocyte hypertrophy; METTL3 expression was induced by Ang II but was downregulated in USP12 knockdown neonatal rat cardiomyocytes (NRCMs)."

reach
"We found that USP12 promoted Ang II-induced cardiomyocyte hypertrophy, and USP12 deficiency attenuated cardiac hypertrophy in mice."

reach
"Our study demonstrated that USP12 promoted Ang II-induced cardiac hypertrophy via regulating METTL3 expression."
USP1 affects 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 ]."
SP1 affects USP12
| 3
SP1 increases the amount of USP12.
| 2
SP1 increases the amount of USP12. 2 / 2
| 2

reach
"In agreement, over-expression of Sp1 enhanced the mRNA levels of USP12 in RAW 264.7 macrophages ( Fig. 1 f) suggesting that LPS induced down-regulation of USP12 at 24 h may be due to depletion of Sp1 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The USP12 mRNA levels in macrophages were enhanced by overexpression of Sp1, and the downregulation of USP12 in 24 h may be related to Sp1 depletion."
SP1 activates USP12.
| 1
SP1 activates USP12. 1 / 1
| 1

reach
"Over-expression of Sp1 and p65 upregulates the promoter activity of USP12."
PPM1B affects USP12
1 | 1 1
1 | 1 1

reach
"The interaction between PPM1B and USP12 was then validated (Fig. 4c), raising the question of whether USP12 deubiquitinates PPM1B."

sparser
"Thus, targeting the USP12-PPM1B cascade may perturb the TME and increase the efficacy of immune checkpoint blockade in certain cancers."

No evidence text available
OPTN affects USP12
| 1 2
| 1 1

reach
"Co-immunoprecipitation confirmed an interaction between Usp12 or Usp12-C48S and Optn."

sparser
"Co-immunoprecipitation confirmed an interaction between Usp12 or Usp12-C48S and Optn (Fig.  xref )."
| 1

sparser
"We have found an intriguing interaction of Usp12 with p62 and Optn, two key receptors necessary for the selective-autophagic clearance of misfolded proteins, mitochondria, and protein aggregates."
USP12 is modified
| 1 2
USP12 is phosphorylated.
| 2
USP12 is phosphorylated. 2 / 2
| 2

sparser
"09; p ‐value USP12  = ."

sparser
"TCR stimulation leads to phosphorylation and translocation of USP12 from the nucleus to the cytosol."
USP12 is deubiquitinated.
| 1
USP12 is deubiquitinated. 1 / 1
| 1

trips
"Deubiquitinating enzyme Usp12 is a novel co-activator of the androgen receptor."
MYC affects USP12
| 3
| 2

sparser
"Western blotting performed using varying concentration of Myc-USP12 to evaluate the dose-dependent expression levels of Bax revealed no increase in the protein levels of Bax when exposed to dose-dependent concentrations of Myc-USP12 ( xref C,D)."

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]"
MYC binds KLF5, USP12, and PARD6B. 1 / 1
| 1

sparser
"These super-enhancer amplifications are associated with over-expression of the MYC oncogene as well as the KLF5 , USP12 and PARD6B genes."
MDK affects USP12
2 | 1
2 | 1

sparser
"Thus, the USP12-MDK axis may be a potential target for breast cancer metastasis treatment [ xref ]."

No evidence text available

No evidence text available
ITCH affects USP12
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
IFI16 affects USP12
| 3
| 3

sparser
"The results showed that the endogenous USP12 formed a stable complex with IFI16 in BMDMs ( xref )."

sparser
"Immunoprecipitation and immunoblot assays were performed to validate whether USP12 interacts with IFI16."

sparser
"Similarly, USP12 interacted with IFI16 in HEK293 cells ( xref )."
FH affects USP12
| 3
| 3

sparser
"Flag-HA tagged USP12 (FH-USP12) can bind with HA-CBP ( xref ) or endogenous CBP ( xref )."

sparser
"The results showed that CBP induced Flag-STAT1 acetylation in vitro , which was gradually inhibited by increasing amounts of FH-USP12 ( xref ), suggesting that USP12 blocks the acetylation effect of CBP on STAT1."

sparser
"We further found that FH-USP12 can interact with HA-p300 in cells ( xref )."
AKT affects USP12
| 3
AKT decreases the amount of USP12.
| 2
AKT decreases the amount of USP12. 2 / 2
| 2

reach
"Consistently, ectopic expression of the myristoylated form of AKT1 (myr-AKT1) significantly repressed USP12 expression in both human and mouse tumour cells (Fig. 1k); knockdown of endogenous AKT1 or AKT2, the two major isoforms of AKT, induced higher levels of USP12 than did the control treatment (Fig. 1l)."

reach
"Furthermore decreasing the levels of Usp12 was shown to sensitize prostate cancer cells to therapeutics which target Akt (McClurg et al., 2014)."
AKT inhibits USP12.
| 1
AKT inhibits USP12. 1 / 1
| 1

reach
"Given that USP12 is negatively regulated by AKT signalling (Fig. 1i–m), we then tested whether restoring the expression of USP12 could counterbalance the activity of AKT in the regulation of chemokine expression."
2 |
Pirinixic acid decreases the amount of USP12. 2 / 2
2 |

No evidence text available

No evidence text available
MHTT affects USP12
| 2
USP12 binds mHTT. 2 / 2
| 2

reach
"Using the available association data for Usp12 and mHTT interactions, we mapped a protein protein interaction network between Usp12 and mHTT, and identified the autophagy receptor Optineurin (Optn) as a potential link."

reach
"The conserved association between USP12 and mHTT is worthy of further investigation aimed at revealing the specific mechanism [151]."
Bisphenol A affects USP12
2 |
Bisphenol A methylates USP12.
1 |
1 |

No evidence text available
Bisphenol A decreases the amount of USP12.
1 |
Bisphenol A decreases the amount of USP12. 1 / 1
1 |

No evidence text available
YAP1 affects USP12
| 1 1
| 1 1

sparser
"Moreover, USP12 interacts with the YAP protein to inhibit its degradation in cancer cells, stabilizing YAP by impeding YAP K48-linked polyubiquitination at the K315 site of YAP ( xref )."

reach
"Additionally, the Co-IP assay confirmed the interaction between USP12 and YAP (Fig. 6B, C)."
WDR48 affects UL138
| 2
| 2

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pY701-STAT1."

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pSTAT1."
WDR48 affects PHLPP1
| 2

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
| 1

sparser
"We confirmed the association of endogenous PHLPP1 with WDR48 and USP12 by immunoprecipitation with PHLPP1 antibody ( xref B )."
| 2

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

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
WDR proteins affects USP12
| 2
WDR proteins binds USP12. 2 / 2
| 2

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
"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."
2 |
2 |

No evidence text available

No evidence text available
Usp12-C48S affects USP12
| 2
USP12 binds Usp12-C48S. 2 / 2
| 2

reach
"An interaction between Usp12 or Usp12-C48S and p62 was also confirmed by co-immunoprecipitation."

reach
"Co-immunoprecipitation confirmed an interaction between Usp12 or Usp12-C48S and Optn."

reach
"Further studies reveal that USP12 stabilizes BCL-10 by deubiquitination and activates the NF-κB signaling pathway, thereby activating CD4 + T cell response."

reach
"In addition, USP12 activates CD4 + T cell proliferation by stabilizing BCL10 and targeting the NF-κB signaling pathway."
USP12 affects mHTT-N586
| 2
USP12 inhibits mHTT-N586. 2 / 2
| 2

reach
"Usp12 nor Usp12-C48S suppressed mHTT-N586 Q138 neurotoxicity during Atg7 knockdown."

reach
"Usp12 knockdown with Usp12-siRNA r did not affect HTT-N586 Q17 survival but increased mHTT-N586 Q138 toxicity."

reach
"Similarly, the knockdown of USP12 decreased IFN-β, CCL5, and IL-6 production in the DNA virus infected-groups but not in the RNA virus infected-group (Fig 2A)."

reach
"Results show that USP12 deficiency significantly inhibited IFN-β, CXCL5, and IL-6 production in BMDMs and MEFs infected with a DNA virus, although not in BMDMs infected with an RNA virus (Figs 1A and S2A)."
| 2

reach
"Moreover, overexpressing USP12 in gastric cancer cell lines enhanced cell migration and invasion, while overexpression of USP12 did not (Fig. 3D, E)."

reach
"Moreover, the transwell assay showed that overexpression of YAP partially restored the cell migration and invasion suppressed by USP12 deletion (Fig. 5E, F)."
USP12 affects WDR proteins
| 2
WDR proteins binds USP12. 2 / 2
| 2

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
"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."
USP12 affects Usp12-C48S
| 2
USP12 binds Usp12-C48S. 2 / 2
| 2

reach
"An interaction between Usp12 or Usp12-C48S and p62 was also confirmed by co-immunoprecipitation."

reach
"Co-immunoprecipitation confirmed an interaction between Usp12 or Usp12-C48S and Optn."
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."
USP12 affects USP12
| 2
USP12 decreases the amount of USP12.
| 1
USP12 decreases the amount of USP12. 1 / 1
| 1

reach
"Negative control siRNA, USP12 siRNA-1, -2 and -3 (20 μM) were transfected into HeLa cells for 48 h. Three of USP12 siRNAs inhibited the expression of USP12 equally."
USP12 activates USP12.
| 1
USP12 activates USP12. 1 / 1
| 1

reach
"After stimulating the TCR with an anti-CD3 antibody, phosphorylation of the USP12 cytoplasmic pool could be induced, allowing USP12 to translocate from the nucleus to the cytoplasm and acted directly on the substrate proteins LAT and Trat1 to stabilize the TCR complex on the T cell surface during signaling."
USP12 affects USP
| 2
USP12 activates USP. 2 / 2
| 2

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)."

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."
USP12 affects TSPYL6
2 |
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No evidence text available

No evidence text available
USP12 affects STAT1
| 2
USP12 phosphorylates STAT1.
| 1
USP12 phosphorylates STAT1. 1 / 1
| 1

reach
"As USP12 has been reported to antagonize PTPN2’s dephosphorylation of pSTAT1, it is also possible that interaction with USP12 contributes to UL138-mediated sustainment of pSTAT1 during HCMV infection."
USP12 deacetylates STAT1.
| 1
USP12 leads to the deacetylation of STAT1. 1 / 1
| 1

reach
"Upon IFN treatment, USP12 accumulates in the nucleus, blocks the CREB-binding protein-induced acetylation of p-STAT1, and thus inhibits the dephosphorylation effects of TCPTP on p-STAT1, which ultimately maintains the nuclear p-STAT1 levels and IFN antiviral efficacy (114)."
USP12 affects RNF19B
2 |
2 |

No evidence text available

No evidence text available
USP12 affects RAD51AP1
2 |

No evidence text available

No evidence text available
USP12 affects Proteasome
| 2
| 2

reach
"Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity, thereby maintaining IFI16 stability and promoting IFI16-STING-IRF3- and p65-mediated antiviral signaling."

reach
"Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity."
USP12 affects Phosphatase
| 2
USP12 deubiquitinates Phosphatase. 1 / 1
| 1

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 deubiquitinates Phosphatase on leucine. 1 / 1
| 1

reach
"For example, USP12 plays a crucial role in prostate cancer (PC) by deubiquitinating the androgen receptor (AR) and the Akt phosphatases, PH domain leucine-rich repeat protein phosphatase (PHLPP) and P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 affects NLRP3
| 2
USP12 increases the amount of NLRP3.
| 1
USP12 increases the amount of NLRP3. 1 / 1
| 1

reach
"Additionally, the study also found out that the UAF1/USP12 and UAF1/USP46 complexes increase p65 expression, which promotes NF-κB activation and increases NLRP3 and IL-1β expression levels."
| PMC
USP12 decreases the amount of NLRP3.
| 1
USP12 decreases the amount of NLRP3. 1 / 1
| 1

reach
"Downregulation of USP12 notably suppressed NLRP3 expression in unstimulated and LPS-stimulated macrophages."
| 2

reach
"Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1."

reach
"Previous studies show that USP12 promotes the growth of multiple myeloma (MM) cells and USP12 knockdown significantly inhibits cell proliferation."
| 2

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

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
USP12 affects MAPK14
| 2
USP12 increases the amount of MAPK14.
| 1
USP12 increases the amount of MAPK14. 1 / 1
| 1

reach
"Overexpressing USP12 increased the mRNA and protein expression of METTL3, as well as MAP3K6 and MAPK14 ( Fig. 3 D and E, Supplementary Fig. 3C and D )."
USP12 activates MAPK14.
| 1
USP12 activates MAPK14. 1 / 1
| 1

reach
"As expected, silencing USP12 decreased the mRNA and protein expression of METTL3, as well as the METTL3-mediated m6A targets (MAP3K6 and MAPK14) ( Fig. 3 B and C, Supplementary Fig. 3A and B )."
USP12 affects ISRE
| 2
USP12 activates ISRE. 2 / 2
| 2

reach
"The exogenous overexpression of USP12 in HEK293T cells promoted DNA-virus induced luciferase activities of IFN-β, ISRE, and NF-κB promoters (Fig 1C)."

reach
"The overexpression of human USP12 promoted DNA virus-induced luciferase activities of IFN-β, ISRE, and NF-κB promoters."
USP12 affects ISGs
| 2
USP12 increases the amount of ISGs. 2 / 2
| 2

reach
"USP12 deficiency also significantly inhibited the expression of ISGs (ISG15, MX1, and IFIT1) in BMDMs and MEFs infected with a DNA or an RNA virus (Figs 1B and S2B)."

reach
"USP12 knockdown also reduced the expression of ISGs (ISG15, MX1, and IFIT1) in both the DNA and RNA virus infected-groups (Fig 2B)."
USP12 affects HYCC1
| 2
USP12 activates HYCC1. 2 / 2
| 2

reach
"Knockdown of USP12 inhibited HCC cell proliferation and promoted apoptosis via the p38-MAPK pathway."

reach
"Besides, USP12 could induce HCC cell cycle arrest at the G2/M phase via the cell cycle protein-dependent kinase 1/cyclinB1 axis."
USP12 affects HSPB9
2 |
2 |

No evidence text available

No evidence text available
USP12 affects H2BC21
1 1 |
USP12 deubiquitinates H2BC21.
1 |
USP12 deubiquitinates H2BC21. 1 / 1
1 |

"<span class="match term0">USP12</span> and USP46 prefer nucleosomal substrates and deubiquitinate both histone H2A and <span class="match term1">H2B</span> in vitro and in vivo"
USP12 binds H2BC21.
1 |
1 |

No evidence text available
USP12 affects H2AC20
1 1 |
USP12 deubiquitinates H2AC20.
1 |
USP12 deubiquitinates H2AC20. 1 / 1
1 |

"<span class="match term0">USP12</span> and USP46 prefer nucleosomal substrates and deubiquitinate both histone <span class="match term1">H2A</span> and H2B in vitro and in vivo"
USP12 binds H2AC20.
1 |
1 |

No evidence text available
USP12 affects GPR161
2 |
2 |

No evidence text available

No evidence text available
USP12 affects GORASP1
2 |
2 |

No evidence text available

No evidence text available
USP12 affects FOXO3
| 1 1
USP12 deubiquitinates FOXO3.
| 1
USP12 deubiquitinates FOXO3. 1 / 1
| 1

reach
"METTL3/YTHDF1-mediated m6A modification stabilizes USP12 to deubiquitinate FOXO3 and promote apoptosis in sepsis-induced myocardial dysfunction."
USP12 binds FOXO3.
| 1
| 1

sparser
"Elevated USP12 interacted with FOXO3, preventing its ubiquitin-mediated degradation, which enhanced FOXO3 binding to the PUMA promoter, leading to upregulation of PUMA."

reach
"Depleting USP12 in hPDLCs led to an accumulation of ubiquitinated proteins, intensifying the ER stress."

reach
"Overall, the results underscore that USP12 KD triggers robust ER stress by elevating the accumulation of ubiquitinated proteins in hPDLCs."
USP12 affects E1
1 1 |
1 1 |

No evidence text available

No evidence text available
USP12 affects Death
| 2
USP12 inhibits Death. 2 / 2
| 2

reach
"USP12 depletion in neurons exacerbated mHTT-mediated toxicity, and overexpression of human USP12 reduced the risk of death associated with mHTT but did not affect the survival of HTT-expressing neurons."

reach
"Usp12 overexpression significantly decreased the risk of death of HDQ109 neurons, but did not affect the survival of control neurons."
| 2

reach
"Knockdown of USP12 causes DNA replication stress and retards tumor growth in vivo and in vitro."

reach
"Knockdown of USP12 causes DNA replication stress and retards tumor growth in vivo and in vitro [126]."
USP12 affects CDC73
2 |
2 |

No evidence text available

No evidence text available
USP12 affects CD274
| 2
USP12 decreases the amount of CD274. 2 / 2
| 2

reach
"Also, USP12 negatively regulated the expression of PD-L1 on MDSCs in colorectal cancer."

reach
"Accordingly, we found that silencing USP12 enhanced PD-L1 expression in tumour cells."
USP12 affects Ang II-induced cardiac hypertrophy
| 2
USP12 activates Ang II-induced cardiac hypertrophy. 2 / 2
| 2

eidos
"Moreover , we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3 , a methyltransferase which catalyze N 6 - methyladenosine ( m 6 A ) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy ."

eidos
"USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo ."
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."
UL138 affects WDR48
| 2
| 2

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pY701-STAT1."

reach
"Although the role of the UL138-UAF1-USP12 complex will be addressed in future studies, the inclusion of USP12 in the IP/MS data set suggests an additional mechanism by which UL138 sustains pSTAT1."
TSPYL6 affects USP12
2 |
2 |

No evidence text available

No evidence text available
TP53 affects USP12
1 | 1
TP53 decreases the amount of USP12.
1 |
TP53 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
TP53 binds USP12.
| 1
| 1

sparser
"However, whether USP12 is associated with P53 in breast cancer remains to be further investigated."
RNF19B affects USP12
2 |
2 |

No evidence text available

No evidence text available
RFX1 affects USP12
2 |
RFX1 decreases the amount of USP12. 2 / 2
2 |

No evidence text available

No evidence text available
RELA affects USP12
| 2
RELA activates USP12. 2 / 2
| 2

reach
"Considering i) USP12 is required for the activation of NFκB pathway ii) USP12 expression is enhanced by LPS (which stimulates NFκB) at earlier time points iii) promoter activity of USP12 is augmented [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Over-expression of Sp1 and p65 upregulates the promoter activity of USP12."
RAD51AP1 affects USP12
2 |

No evidence text available

No evidence text available
PHLPP1 affects WDR48
| 2

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
| 1

sparser
"We confirmed the association of endogenous PHLPP1 with WDR48 and USP12 by immunoprecipitation with PHLPP1 antibody ( xref B )."
NES affects USP12
| 2
NES inhibits USP12.
| 1
NES inhibits USP12. 1 / 1
| 1

reach
"Importantly, by disrupting the interaction with WDR20, “NES” mutations abrogate WDR20-induced relocation of USP12 to the PM (Additional File 3), and would also prevent its full catalytic activation.Th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
NES activates USP12.
| 1
NES activates USP12. 1 / 1
| 1

reach
"Importantly, by disrupting the interaction with WDR20, “NES” mutations abrogate WDR20-induced relocation of USP12 to the PM (Additional File 3), and would also prevent its full catalytic activation.Th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 2

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

sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
MMP14 affects USP12
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2 |

No evidence text available

No evidence text available
Infections affects USP12
| 2
Infections increases the amount of USP12. 2 / 2
| 2

reach
"To explore the potential role of USP12 in antiviral immunity, we first detected the expression of USP12 after virus infection and found that USP12 expression was induced by HSV-1 infection (S1A and S1B Fig), which was mainly regulated by NF-κB p65 and IRF3, but not by STAT1 (S1C and S1D Fig)."

reach
"The prior study revealed that Leishmania braziliensis infection up-regulated the expression of the USP12 in macrophage cells [35]."
HSPB9 affects USP12
2 |
2 |

No evidence text available

No evidence text available
GPR161 affects USP12
2 |
2 |

No evidence text available

No evidence text available
GORASP1 affects USP12
2 |
2 |

No evidence text available

No evidence text available
EBNA3 affects USP12
| 2
EBNA3 binds USP12.
| 1
| 1

reach
"EBNA3A can bind to RBPJ, a Notch pathway protein, and USP46/USP12 or CtBP ."
EBNA3 activates USP12.
| 1
EBNA3 activates USP12. 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."
E1 affects USP12
1 1 |
1 1 |

No evidence text available

No evidence text available
CXCL1 affects USP12
| 2
CXCL1 inhibits USP12.
| 1
CXCL1 inhibits USP12. 1 / 1
| 1

reach
"Moreover, coexpression of Cxcl1 and Ccl2 efficiently attenuated activation of CD8 and CD4 T cells in tumour cells ectopically expressing USP12, as evidenced by the changes in the frequencies of TNF-α IFN-γ cells in the populations (Fig. 5g)."
CXCL1 increases the amount of USP12.
| 1
CXCL1 increases the amount of USP12. 1 / 1
| 1

reach
"Similarly, co-expression of Cxcl1 and Ccl2 in 889-S1 tumour cells substantially increased tumour incidence and growth in the presence of USP12 overexpression (Fig. 3g), suggesting the importance of the tumour-extrinsic effects controlled by USP12."
CDC73 affects USP12
2 |
2 |

No evidence text available

No evidence text available
2 |
17beta-estradiol increases the amount of USP12. 2 / 2
2 |

No evidence text available

No evidence text available
Vorinostat affects USP12
1 |
Vorinostat decreases the amount of USP12. 1 / 1
1 |

No evidence text available
Urethane affects USP12
1 |
Urethane increases the amount of USP12. 1 / 1
1 |

No evidence text available

No evidence text available
1 |
Trichloroethene decreases the amount of USP12. 1 / 1
1 |

No evidence text available
Transmitting long-range allosteric signal BL1 affects USP12
| 1
Transmitting long-range allosteric signal BL1 activates USP12. 1 / 1
| 1

eidos
"UAF1 activates USP12 by binding to the tip of its Fingers domain and transmitting a long-range allosteric signal to BL1 ."
Tme affects USP12
| 1
| 1

sparser
"Studies have illustrated that USP12 was associated with many aspects of TME, including immune checkpoints, chemokines, immune cells and viral infection [ xref – xref ]."
Thiram affects USP12
1 |
Thiram increases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Testosterone decreases the amount of USP12. 1 / 1
1 |

No evidence text available
Sunitinib affects USP12
1 |
Sunitinib increases the amount of USP12. 1 / 1
1 |

No evidence text available
Substrate affinity affects USP12
| 1
Substrate affinity activates USP12. 1 / 1
| 1

eidos
"First , our results rule out the possibility that UAF1 and WDR20 activate USP12 by enhancing its substrate affinity ."
1 |
Sodium arsenite increases the amount of USP12. 1 / 1
1 |

No evidence text available
Sirolimus affects USP12
| 1
Sirolimus decreases the amount of USP12. 1 / 1
| 1

reach
"Treatment with inhibitors targeting MEK (U0126), ERK (ERK inhibitor), JNK (JNK inhibitor II), JAK-STAT3 (WP1066), c-Myc (c-Myc inhibitor), p38 MAPK (SB203580), and TGF-β-SMAD (SB431542 and SIS3) failed to produce a substantial change in USP12 expression (Supplementary Fig. 1e); however, blocking AKT-mTOR signalling using the selective AKT inhibitor API-2 or the mTOR inhibitor rapamycin significantly increased USP12 expression (Fig. 1i, j)."
1 |
Silicon dioxide decreases the amount of USP12. 1 / 1
1 |

No evidence text available
Rotenone affects USP12
1 |
Rotenone increases the amount of USP12. 1 / 1
1 |

No evidence text available
Potassium chromate decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |

No evidence text available
1 |

No evidence text available
Paracetamol affects USP12
1 |
Paracetamol increases the amount of USP12. 1 / 1
1 |

No evidence text available
Pan affects USP12
| 1
Pan acetylates USP12. 1 / 1
| 1

sparser
"Intriguingly, we found that USP12 significantly inhibited CBP-mediated pan-acetylation effects in cells."
Oxycodone affects USP12
1 |
Oxycodone decreases the amount of USP12. 1 / 1
1 |

No evidence text available
Optimizing catalytic cleft affects USP12
| 1
Optimizing catalytic cleft activates USP12. 1 / 1
| 1

eidos
"These results strongly suggest that WDR20 can activate USP12 by allosterically optimizing its catalytic cleft , whereas the effect of UAF1 binding cannot be directly transmitted to the catalytic cysteine through USP12 ."
1 |
Okadaic acid increases the amount of USP12. 1 / 1
1 |

No evidence text available
Mutation Ub globular domain-binding residue BL1 affects USP12
| 1
Mutation Ub globular domain-binding residue BL1 activates USP12. 1 / 1
| 1

eidos
"Finally , consistent with the expected substrate-induced interactions between Ub and BL1 of USP12 in all forms , mutation of a Ub globular domain-binding residue on BL1 , Y264 , compromised the ability of both UAF1 and WDR20 to activate USP12 for Ub-AMC hydrolysis ( Figures 6D , 6E , and S5F ) ."
Medroxyprogesterone acetate increases the amount of USP12. 1 / 1
1 |

No evidence text available
| 1
MTOR inhibitor decreases the amount of USP12. 1 / 1
| 1

reach
"Treatment with inhibitors targeting MEK (U0126), ERK (ERK inhibitor), JNK (JNK inhibitor II), JAK-STAT3 (WP1066), c-Myc (c-Myc inhibitor), p38 MAPK (SB203580), and TGF-β-SMAD (SB431542 and SIS3) failed to produce a substantial change in USP12 expression (Supplementary Fig. 1e); however, blocking AKT-mTOR signalling using the selective AKT inhibitor API-2 or the mTOR inhibitor rapamycin significantly increased USP12 expression (Fig. 1i, j)."

reach
"In summary, we show that USP12 levels are altered in LPS stimulated macrophages and USP12 functions to selectively augment the pro-inflammatory responses of LPS-induced macrophages."
Leflunomide affects USP12
1 |
Leflunomide increases the amount of USP12. 1 / 1
1 |

No evidence text available
Lead atom affects USP12
1 |
Lead atom increases the amount of USP12. 1 / 1
1 |

No evidence text available
Jinfukang affects USP12
1 |
Jinfukang decreases the amount of USP12. 1 / 1
1 |

No evidence text available
Ionomycin affects USP12
1 |
Ionomycin increases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hypochlorous acid increases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4533 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4476 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4447 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4271 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-9500 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-92a-2-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-8083 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-744-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6887-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6885-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6876-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6795-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6780b-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-625-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-5196-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4747-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4725-3p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4472 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-373-3p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-328-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3202 decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-215-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-192-5p decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Formaldehyde increases the amount of USP12. 1 / 1
1 |

No evidence text available
Folic acid affects USP12
1 |
Folic acid increases the amount of USP12. 1 / 1
1 |

No evidence text available
Doxorubicin affects USP12
1 |
Doxorubicin decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Deltamethrin increases the amount of USP12. 1 / 1
1 |

No evidence text available
| 1

reach
"Besides, our previous data showed that USP12 could regulate the expression of METTL3 mRNA ( Fig. 3 B and D), and we also found that cycloheximide (CHX, an inhibitor for protein biosynthesis) abolished[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Cre affects USP12
| 1
Cre binds USP12. 1 / 1
| 1

sparser
"However, after exclusion of samples in which CNVs overlay the gene itself, amplification of the CRE was not associated with differential expression of USP12 or any other gene in the proximity of the CNV segments ( xref , xref )."
Clofibrate affects USP12
1 |
Clofibrate increases the amount of USP12. 1 / 1
1 |

No evidence text available
Cisplatin affects USP12
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Cisplatin decreases the amount of USP12. 1 / 1
1 |

No evidence text available
| 1

sparser
"USP12 interacted with viral capsid protein (CP) in Epinephelus coioides to inhibit viral infection and positively regulated the levels of associated inflammatory factors, including TNF-α, IL-1β, IL-6, IL-8, IRF, and IRF7 [ xref ]."
Bun107 affects USP12
| 1
Bun107 activates USP12. 1 / 1
| 1

reach
"Moreover, the human ortholog of Bun107 activates USP12 and USP46 XREF_BIBR."
Bucladesine affects USP12
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Bucladesine increases the amount of USP12. 1 / 1
1 |

No evidence text available
Bisphenol F affects USP12
1 |
Bisphenol F increases the amount of USP12. 1 / 1
1 |

No evidence text available
Binding tip Fingers domain affects USP12
| 1
Binding tip Fingers domain activates USP12. 1 / 1
| 1

eidos
"UAF1 activates USP12 by binding to the tip of its Fingers domain and transmitting a long-range allosteric signal to BL1 ."
1 |
Beta-D-glucose decreases the amount of USP12. 1 / 1
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No evidence text available
1 |
1 |

No evidence text available
Avobenzone affects USP12
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Avobenzone increases the amount of USP12. 1 / 1
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No evidence text available
Aristolochic acid A decreases the amount of USP12. 1 / 1
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No evidence text available
1 |
Aluminium atom increases the amount of USP12. 1 / 1
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No evidence text available
All-trans-retinoic acid decreases the amount of USP12. 1 / 1
1 |

No evidence text available
1 |
Aflatoxin B1 demethylates USP12. 1 / 1
1 |

No evidence text available
Abrine affects USP12
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Abrine increases the amount of USP12. 1 / 1
1 |

No evidence text available
ZAP70 affects USP12
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1 |

No evidence text available
YWHAH affects USP12
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1 |

No evidence text available
WDR77 affects USP12
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1 |

No evidence text available
WDR48-WDR20 affects USP12
| 1
USP12 binds WDR48-WDR20. 1 / 1
| 1

reach
"Binding of USP12 to WDR48-WDR20 is essential to maintain Itgb1 surface levels."
WDR48 affects F219
| 1
WDR48 binds USP12 and F219. 1 / 1
| 1

reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
WDR26 affects USP12
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1 |

No evidence text available
WDR20 affects PHLPP2
| 1
| 1

sparser
"Both Usp12 and WDR20 alone were able to interact with both PHLPP (Figure xref ) and PHLPPL (Figure xref )."
WDR20 affects DMWD
| 1
USP12 binds DMWD and WDR20. 1 / 1
| 1

sparser
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
WDR20 affects 293 T
| 1
WDR20 binds USP12 and 293 T. 1 / 1
| 1

reach
"We generated YFP-USP12 V279D/F287A and Myc-WDR20 F262A/W306A mutants and confirmed that these mutations largely or completely abrogate WDR20 binding to USP12 in 293 T cells ( Fig. 4 a)."
WD40-repeat-containing protein affects USP12
| 1
WD40-repeat-containing protein activates USP12. 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 ) ."
Vincristine affects USP12
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Vincristine increases the amount of USP12. 1 / 1
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No evidence text available
Ubiquitin affects USP12
| 1

sparser
"Interestingly, it has been shown that USP12-Ub and UAF1 have two possible binding sites: The Finger domain and the back of the ubiquitin-binding cleft [ xref ]."

eidos
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20 Ubiquitin-specific proteases ( USPs ) constitute the largest family of deubiquitinating enzymes , whose catalytic competency is often modulated by their binding partners through unknown mechanisms ."
USP46 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."
USP46 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."
USP39 affects USP12
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1 |

No evidence text available
USP12 affects tumor growth
| 1
USP12 activates tumor growth. 1 / 1
| 1

eidos
"Downregulation of USP12 inhibits tumor growth via the p38 / MAPK pathway in hepatocellular carcinoma ."
USP12 affects transport
| 1
| 1

reach
"Specifically silencing USP12 impedes the transport of Notch to lysosomes, resulting in an increase in cell surface receptors and heightened Notch activity."
| 1
| 1

reach
"Thus, USP12 and OTUD7B counterbalance inhibitory E3 ligases to stabilize TCR signaling.Aside from acting at the proximal signalosome, E3 ligases also inhibit T-cell activation by acting further downstream, controlling the key transduction events that lead to the nuclear translocation of the T-cell activating transcription factors."
| PMC
USP12 affects transcription downstream METTL3
| 1
USP12 activates transcription downstream METTL3. 1 / 1
| 1

eidos
"Mechanistically , USP12 binds and stabilizes p300 , thereby activating the transcription of its downstream gene METTL3 ."
USP12 affects tme
| 1
| 1

sparser
"Studies have illustrated that USP12 was associated with many aspects of TME, including immune checkpoints, chemokines, immune cells and viral infection [ xref – xref ]."
USP12 affects receptor complex
| 1
USP12 activates receptor complex. 1 / 1
| 1

reach
"It has been also shown that USP12 deubiquitylated and prevented lysosomal degradation of T-cell receptor complex (TCR) to sustain TCR mediated signaling [ 20 ]."
USP12 affects pathways
| 1
USP12 activates pathways. 1 / 1
| 1

sparser
"In contrast, USP12, USP34, and MYSM1 abnormally activated the ubiquitin ligase pathways ( xref )."
| 1
| 1

reach
"Furthermore, USP12 contributed to the pathogenesis of Ang–II–induced cardiac hypertrophy via enhancing the p300/METTL3 axis."
USP12 affects p38
| 1
USP12 leads to the phosphorylation of p38. 1 / 1
| 1

reach
"Further, USP12 knockdown suppressed LPS-induced phosphorylation of ERK1/2 and p38 MAPKs which are required for LPS-induced NFκB activation [8] ."
| 1
USP12 decreases the amount of nitric oxide. 1 / 1
| 1

reach
"USP12 deficiency promoted the expression of inducible nitric oxide synthase (iNOS) in MDSCs by inhibiting the p65-NF-κB signaling pathway, and MDSCs with high iNOS expression inhibit T-cell function, resulting in poorer tumor response to chemotherapy [86]."
USP12 affects marker) protein
| 1
USP12 increases the amount of marker) protein. 1 / 1
| 1

reach
"Moreover, the knockdown of USP12 reduces the ability of lung metastasis and CD31 (vascular endothelial cell marker) protein levels in mice with breast cancer."

reach
"We also investigated whether USP12 expression in tumour cells might modulate macrophage polarization."
USP12 affects function monocytic MDSCs
| 1
USP12 activates function monocytic MDSCs. 1 / 1
| 1

eidos
"In the present study , we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic ( M ) - MDSCs , resulting in increased CD8 + T cell response and decelerated tumor growth ."
USP12 affects function M-MDSCs
| 1
USP12 activates function M-MDSCs. 1 / 1
| 1

eidos
"Furthermore , USP12 deficiency inhibited the suppressor function of M-MDSCs by downregulating the negative regulatory molecules iNOS and PD-L1 , through deubiquitinating and stabilizing p65 ."

reach
"Gene ontology (GO) analysis revealed that the pathways significantly enriched in USP12-downregulated genes were mostly related to cytokine-mediated signalling pathway and immune effector process (Fig. 3a); further in-depth examination showed that USP12 expression decreased levels of a number of chemokine, such as CXCL8, CXCL1, CXCL2, CCL2 and CCL5, most of which were associated with immune cell recruitment (Fig. 3b and Supplementary Fig. 2a)."
USP12 affects cre
| 1
Cre binds USP12. 1 / 1
| 1

sparser
"However, after exclusion of samples in which CNVs overlay the gene itself, amplification of the CRE was not associated with differential expression of USP12 or any other gene in the proximity of the CNV segments ( xref , xref )."
USP12 affects clonogenicity
| 1
USP12 activates clonogenicity. 1 / 1
| 1

eidos
"Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy ."

reach
"USP12 negatively regulates protumourigenic chemokine production."

reach
"Transient depletion of USP12, USP46, and USP53 did not induce a senescence arrest."
USP12 increases the amount of cell cycle protein. 1 / 1
| 1

reach
"In the aspect of cell biogenesis, USP12 promotes cell cycle progression by upregulating the transcription of BMI-1, c-Myc, and cell cycle protein D2 [50]."
| 1

sparser
"USP12 interacted with viral capsid protein (CP) in Epinephelus coioides to inhibit viral infection and positively regulated the levels of associated inflammatory factors, including TNF-α, IL-1β, IL-6, IL-8, IRF, and IRF7 [ xref ]."
USP12 affects bortezomib
| 1
| 1

reach
"Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1."
USP12 affects ZAP70
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1 |

No evidence text available
USP12 affects YWHAH
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1 |

No evidence text available
USP12 affects WDR77
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1 |

No evidence text available
USP12 affects WDR48.USP12 complex
| 1
USP12 activates WDR48.USP12 complex. 1 / 1
| 1

reach
"In fact, overexpression of WDR48 and USP12 together with PHLPP1 resulted in reduction of Akt phosphorylation, supporting the synergistic effect of the WDR48.USP12 complex along with PHLPP1 in suppressing Akt signaling (XREF_FIG D)."
USP12 affects WDR48-WDR20
| 1
USP12 binds WDR48-WDR20. 1 / 1
| 1

reach
"Binding of USP12 to WDR48-WDR20 is essential to maintain Itgb1 surface levels."
USP12 affects WDR26
1 |
1 |

No evidence text available
USP12 affects VSV-
| 1
USP12 activates VSV-. 1 / 1
| 1

reach
"The overexpression of USP12 in BMDMs promoted the expressions of ISG15 and MX1 in both VSV- and HSV-1-infected BMDMs (S4C and S4D Fig) and reduced the replication of VSV and HSV-1, as indicated by the RNA levels (S4E Fig) and viral titers (S4F 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 USP39
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1 |

No evidence text available
USP12 affects UPR-related genes
| 1
USP12 decreases the amount of UPR-related genes. 1 / 1
| 1

reach
"USP12 knockdown significantly elevated the mRNA and protein levels of UPR-related genes, a change further pronounced in the presence or absence of TG ( Fig. 5 A and B )."
USP12 affects UBC
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1 |

No evidence text available
USP12 affects UAF
| 1
USP12 binds UAF. 1 / 1
| 1

reach
"A previous report states that USP12 and UAF form a complex with an enzymatic effect, after which the enzymatic effect of USP12 and UAF complex on target protein is stimulated by WDR20 [37,38]."
USP12 affects Th1 Cells
| 1
| 1

reach
"Furthermore, USP12 exerts a positive regulatory effect within cells and modulates T-helper 1 (Th1) and Th17 cells through intrinsic mechanisms [17]."
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

reach
"Thus, USP12 and OTUD7B counterbalance inhibitory E3 ligases to stabilize TCR signaling.Aside from acting at the proximal signalosome, E3 ligases also inhibit T-cell activation by acting further downstream, controlling the key transduction events that lead to the nuclear translocation of the T-cell activating transcription factors."
| PMC
USP12 affects Snail1
| 1
USP12 increases the amount of Snail1. 1 / 1
| 1

reach
"When these DUBs were co-expressed with Snail1 in HEK293 cells, we found that USP12, Dub3 and USP28 significantly increased Snail1 levels, similar to results obtained when cells were treated with the proteasome inhibitor MG132 (XREF_SUPPLEMENTARY)."
USP12 affects Sf9
| 1
USP12 increases the amount of Sf9. 1 / 1
| 1

reach
"USP1, USP12, and UAF1 were produced using Sf9 and Sf21 insect cell expression."
USP12 affects SGO1
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1 |

No evidence text available
USP12 affects SDF4
1 |
1 |

No evidence text available
USP12 affects S2B
| 1
USP12 increases the amount of S2B. 1 / 1
| 1

reach
"USP12 deficiency also significantly inhibited the expression of ISGs (ISG15, MX1, and IFIT1) in BMDMs and MEFs infected with a DNA or an RNA virus (Figs 1B and S2B)."
USP12 affects RAF1
1 |
1 |

No evidence text available
USP12 affects PNMA2
1 |
1 |

No evidence text available
USP12 affects PHLPP1.WDR48
| 1
PHLPP1.WDR48 binds USP12. 1 / 1
| 1

reach
"We further confirmed the existence of a specific PHLPP1.WDR48 and USP12 complex in vivo by demonstrating that WDR48 and USP12 but not other WD repeat protein WDR5 co-immunoprecipitated with exogenously expressed PHLPP1 in 293T cells (XREF_FIG D)."
USP12 affects PDCD1
| 1
USP12 activates PDCD1. 1 / 1
| 1

reach
"Downregulation of USP12 also promotes NSCLC angiogenesis and upregulates PD-1 thus inducing resistance to anti-PD-L1 therapy [66]."
USP12 affects PARD6B
| 1
MYC binds KLF5, USP12, and PARD6B. 1 / 1
| 1

sparser
"These super-enhancer amplifications are associated with over-expression of the MYC oncogene as well as the KLF5 , USP12 and PARD6B genes."
USP12 affects PAIP1
1 |
1 |

No evidence text available
USP12 affects P53-MDM2-AR-AKT
| 1
USP12 activates P53-MDM2-AR-AKT. 1 / 1
| 1

reach
"In prostate cancer, USP12 could also modulate P53-MDM2-AR-AKT signaling [31]."
USP12 affects OPN1LW
| 1
USP12 leads to the deacetylation of OPN1LW. 1 / 1
| 1

reach
"Moreover, ubiquitin specific peptidase 12 (USP12) inhibited CBP- mediated acetylation and maintained nuclear p-STAT1 and subsequent dephosphorylation of p-STAT1 in the nucleus (54)."
USP12 affects NUP160
1 |
1 |

No evidence text available
USP12 affects NOTCH1
1 |
1 |

No evidence text available
USP12 affects NOTCH receptors
| 1
USP12 decreases the amount of NOTCH receptors. 1 / 1
| 1

reach
"USP12 deficiency can lead to increased expression of inactive NOTCH receptors on the cell membrane, which in turn promotes NOTCH signaling activation."
USP12 affects NMRAL1
1 |
1 |

No evidence text available
USP12 affects Mice
| 1
USP12 activates Mice. 1 / 1
| 1

reach
"Exogenous USP12 expression markedly increased the survival of mice and decreased overall tumour number or burden in the entire lung compared with that of control mice (Fig. 2a–c)."
USP12 affects MX1
| 1
USP12 increases the amount of MX1. 1 / 1
| 1

reach
"The overexpression of USP12 in BMDMs promoted the expressions of ISG15 and MX1 in both VSV- and HSV-1-infected BMDMs (S4C and S4D Fig) and reduced the replication of VSV and HSV-1, as indicated by the RNA levels (S4E Fig) and viral titers (S4F Fig)."
USP12 affects MTLL3
| 1
USP12 activates MTLL3. 1 / 1
| 1

reach
"According to a recent study, USP12 (ubiquitin-specific protease 12) via enhancing p300/MTLL3 axis promote myocardial hypertrophy [61], and our finding may indicate the possibility of m A methylation and ubiquitination cooperatively regulate heart growth."
USP12 affects MECP2
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1 |

No evidence text available
USP12 affects MDM2-P53
| 1
USP12 leads to the ubiquitination of MDM2-P53. 1 / 1
| 1

reach
"Prior studies suggested a role of USP12 in prostate carcinomas, wherein USP12 promoted AR signalling and tumour cell proliferation, as well as therapy resistance, by regulating AR ubiquitination and MDM2-P53 signalling ."
USP12 affects MAP3K6
| 1
USP12 increases the amount of MAP3K6. 1 / 1
| 1

reach
"Overexpressing USP12 increased the mRNA and protein expression of METTL3, as well as MAP3K6 and MAPK14 ( Fig. 3 D and E, Supplementary Fig. 3C and D )."
USP12 affects KLK3
| 1
USP12 increases the amount of KLK3. 1 / 1
| 1

reach
"For example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation; 17 USP12 stabilizes AR, enhances its cellular function, and thereby triggers the gene expression of PSA."
USP12 affects KLF5
| 1
MYC binds KLF5, USP12, and PARD6B. 1 / 1
| 1

sparser
"These super-enhancer amplifications are associated with over-expression of the MYC oncogene as well as the KLF5 , USP12 and PARD6B genes."
USP12 affects KIAA1549L
| 1
| 1

eidos
"In vivo experiments showed that USP12-knockdown could suppress tumor growth in mice , and immuno-blotting revealed that USP12 could induce G2 / M arrest through the cyclin dependent kinase 1 / cyclinB1 axis , and trigger apoptosis via the p38 / mitogen-activated protein kinase pathway ."
USP12 affects Infections
| 1
| 1

reach
"Overexpression of USP12 inhibited vesicular stomatitis virus (VSV) infection, while knockdown of USP12 remarkably promoted VSV or influenza A virus (H1N1) infection."
USP12 affects ISRE promoter
| 1
USP12 activates ISRE promoter. 1 / 1
| 1

reach
"By contrast, USP12 enhanced IFN-β, NF-κB, and ISRE promoter activities in a dose-dependent manner after cotransfection with IFI16 (Fig 4B)."
USP12 affects ISG65
| 1
USP12 increases the amount of ISG65. 1 / 1
| 1

reach
"UbH1 knockdown reduced ISG75 but not ISG65 expression (XREF_FIG), suggesting that deubiquitination by UbH1 specifically affects ISG75 copy number; clearly this mimics the direct effect of RNAi against ISG75."
USP12 affects ISG15
| 1
USP12 increases the amount of ISG15. 1 / 1
| 1

reach
"The overexpression of USP12 in BMDMs promoted the expressions of ISG15 and MX1 in both VSV- and HSV-1-infected BMDMs (S4C and S4D Fig) and reduced the replication of VSV and HSV-1, as indicated by the RNA levels (S4E Fig) and viral titers (S4F Fig)."
USP12 affects IRF3
| 1
USP12 leads to the dephosphorylation of IRF3. 1 / 1
| 1

reach
"After STING activation, TBK1 is recruited and activated to induce the activation of downstream IRF3 and NF-κB. Further evaluations showed that USP12 deficiency decreased the phosphorylation of p65 and IRF3 induced by HSV-1 (S7A Fig) but not by VSV (S7B Fig)."
USP12 affects IRAK4
| 1
| 1

sparser
"Therefore, targeted regulation the activation of USP12-IRAK4 axis is a potential therapeutic strategy for the LPS-induced sepsis treatment."
USP12 affects ILF3
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1 |

No evidence text available
USP12 affects IGDCC4
1 |
1 |

No evidence text available

reach
"In Huntington's disease, USP12 induces neuronal autophagy to rescue mHTT-mediated neurodegeneration [ 10 ]."
USP12 affects Hippo
| 1
USP12 activates Hippo. 1 / 1
| 1

reach
"Notably, USP12 depletion was found to inhibit gastric cancer progression via the Hippo/YAP axis, whereas USP12 overexpression exhibited the opposite effect, promoting gastric cancer growth and enhancing YAP activity."
| 1

reach
"In addition, USP12 deficiency largely attenuated cellular antiviral ability against VSV, Sendai virus (SeV) and herpes simplex virus (HSV) [ 18 ]."
USP12 affects HTT
| 1
USP12 inhibits HTT. 1 / 1
| 1

reach
"We propose a mechanism by which Usp12 suppresses HD related neurodegeneration via induction of autophagy."
USP12 affects HTT fragments
| 1
USP12 activates mutated HTT fragments. 1 / 1
| 1

reach
"A study in yeast found that Ubp13, the yeast orthologue of USP12, enhances the toxicity of mutant HTT fragments (Willingham et al., 2003)."
USP12 affects HNRNPH1
1 |
1 |

No evidence text available
USP12 affects HMGB1-mediated autophagy
| 1
USP12 activates HMGB1-mediated autophagy. 1 / 1
| 1

eidos
"Knockdown of USP12 decreased the level of HMGB1 and suppressed HMGB1-mediated autophagy in MM ."
USP12 affects HIPPO
| 1
USP12 activates HIPPO. 1 / 1
| 1

reach
"Taken together, these findings indicate that USP12 can activate HIPPO/YAP signaling, with this effect being dependent on its deubiquitinating enzyme activity."
USP12 affects H2BK120ub
| 1
USP12 deubiquitinates H2BK120ub. 1 / 1
| 1

reach
"Other major DUBs with specificity for histone H2AK119ub over H2BK120ub are BAP1 and USP16, while USP3, USP12, USP22, and USP44 deubiquitinate both H2AK119ub and H2BK120ub, as well as different non histone substrates [XREF_BIBR]."
USP12 affects H2BC10
1 |
USP12 deubiquitinates H2BC10. 1 / 1
1 |

"It was shown that <span class="match term0">USP12</span> deubiquitinates histones H2A and <span class="match term1">H2B</span> both in vitro and in vivo"
USP12 affects H2AC17
1 |
USP12 deubiquitinates H2AC17. 1 / 1
1 |

"It was shown that <span class="match term0">USP12</span> deubiquitinates histones <span class="match term1">H2A</span> and H2B both in vitro and in vivo"
USP12 affects GRIA1
| 1
USP12 decreases the amount of GRIA1. 1 / 1
| 1

reach
"Knock-down of USP46, but not USP12, results in increased levels of ubiquitinated GluA1, decreased surface and total levels of GluA1, and reduced mEPSC amplitudes, consistent with a role for USP46 in deubiquitinating mammalian AMPARs."
USP12 affects GRB2
1 |
1 |

No evidence text available
USP12 affects GPR12
| 1
| 1

sparser
"Three SNPs (SBNO2 rs2024092, CARD9 rs10781499, and rs17085007 between GPR12-USP12) were significantly associated with increased UC risk while NKX2-3 rs4409764 was a significant protective factor."
USP12 affects GEM
| 1
| 1

sparser
"Escherichia coli DH5ɑ harboring the pGEM-USP12 clone was cultured to prepare recombinant plasmid DNA using a Mini Prep kit (Qiagen, Germany)."
USP12 affects GATD3
1 |
1 |

No evidence text available
USP12 affects G1 phase
| 1
| 1

reach
"Depletion of USP12 decreased PC cell proliferation, increased apoptosis and caused G 1 arrest ( Burska et al., 2013 and McClurg et al., 2014 )."
USP12 affects G0/G1
| 1
USP12 inhibits G0/G1. 1 / 1
| 1

reach
"Furthermore, PI staining by flow cytometry analysis revealed that USP12 deletion significantly increased G0/G1 phase cell proliferation (Fig. 2H–K)."
USP12 affects Flag
| 1
| 1

sparser
"The transfection of Flag-USP12 was achieved in a dose-dependent manner to identify USP12 as a stabilizer for Bax."
USP12 affects FLT4
| 1
USP12 increases the amount of FLT4. 1 / 1
| 1

reach
"USP12 can also activate the Akt signaling pathway in tumors and endothelial cells by upregulating MDK, and promoting VEGFR3 expression through the mTOR signaling pathway, which then promotes the occurrence and progression of breast cancer [73]."
USP12 affects F219
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WDR48 binds USP12 and F219. 1 / 1
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"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
USP12 affects ERK
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USP12 leads to the phosphorylation of ERK. 1 / 1
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"Further, USP12 knockdown suppressed LPS-induced phosphorylation of ERK1/2 and p38 MAPKs which are required for LPS-induced NFκB activation [8] ."
USP12 affects EPHA2
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No evidence text available
USP12 affects EGFP
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sparser
"Since EGFP-USP12 was absent from FAs (Fig.  xref ) and the members of the USP12/46-WDRs complex were also undetectable in the integrin adhesome (Horton et al, xref ; Kuo et al, xref ; Schiller et al, xref ), we conclude that the USP12/46-WDRs complex binds Itgb1 on endosomes and not in FAs."
USP12 affects EBNA3
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"EBNA3A can bind to RBPJ, a Notch pathway protein, and USP46/USP12 or CtBP ."
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sparser
"Interestingly, Cbl-b and Itch were isolated among the E3 ligases interacting with USP12."
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reach
"USP12 inhibits mHTT neurotoxicity independent of its deubiquitinase activity."

sparser
"In xref , we visualized the top 50 negatively correlated expression genes, and the top five are presented in the form of scatter plots in xref : AL355075.4 ( r = -0.459), AC087286.1 ( r = - 0.558), AC100800.1 ( r = -0.534), ZBTB20-AS5 ( r = -0.534), and USP12-AS1 ( r = -0.566), all with P -value <0.001."

reach
"What's more, the luciferase reporter gene assay showed that silencing USP12 inhibited the transcription activity of METTL3 promoter ( Supplementary Fig. 4D ), while overexpressing USP12 promoted the t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP12 affects DHX8
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No evidence text available
USP12 affects DCAF4
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No evidence text available
| 1

eidos
"In addition , USP12 promotes cell survival , proliferation , tumorigenesis , and cell cycle progression by upregulating BMI-1 , c-Myc , and cyclin D2 [ 24,25,26,27 ] ."
USP12 affects CX3CL1
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No evidence text available
USP12 affects CTNNB1
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USP12 increases the amount of CTNNB1. 1 / 1
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"Likewise, depletion of USP12, USP7, or FBXO36 increased total cellular levels of beta-catenin."
USP12 affects CLASP2
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No evidence text available
USP12 affects CD8
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USP12 inhibits CD8. 1 / 1
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"Hence, targeting USP12 might reduce the activity of MDSCs and further restore CD8 T-cell cytotoxicity to synergize with ICB."
USP12 affects CD6
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No evidence text available
USP12 affects CD4+
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USP12 activates CD4+. 1 / 1
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"USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10."
USP12 affects CCL5
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USP12 activates CCL5. 1 / 1
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"Similarly, the knockdown of USP12 decreased IFN-β, CCL5, and IL-6 production in the DNA virus infected-groups but not in the RNA virus infected-group (Fig 2A)."
USP12 affects CBLB
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No evidence text available
USP12 affects CASC3
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USP12 activates CASC3. 1 / 1
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"USP12 depletion, concomitant with a reduced expression of HMGB1, suppressed autophagy and increased the sensitivity of resistant cells to BTZ."
USP12 affects CADM1
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USP12 inhibits CADM1. 1 / 1
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"This concept is best illustrated by the related DUBs USP1, USP12, and USP46, which are inhibited by blocking loop 1 (BL1) and BL2 ( Figure 4 B)."
USP12 affects BMI1
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USP12 increases the amount of BMI1. 1 / 1
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"In the aspect of cell biogenesis, USP12 promotes cell cycle progression by upregulating the transcription of BMI-1, c-Myc, and cell cycle protein D2 [50]."
USP12 affects Ang II-induced myocardial hypertrophy
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USP12 inhibits Ang II-induced myocardial hypertrophy. 1 / 1
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eidos
"Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy , while overexpression of USP12 have the opposite effect ."
USP12 affects Ad
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sparser
"On the other hand, we transfected USP12 overexpression adenovirus (Ad-USP12) into NRCMs to increase the expression of USP12 ( Fig. 2 E)."
USP12 affects APP
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No evidence text available
USP12 affects AKT1
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USP12 activates AKT1. 1 / 1
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"On the other hand, USP12 can also stabilize AR proteins and enhance their transcriptional activity by stabilizing the AKT (protein kinase B) dephosphorylases (PHLPP and PHLPPL) (McClurg et al., 2014)."
USP12 affects AKT-mTOR
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USP12 inhibits AKT-mTOR. 1 / 1
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"Deletion analysis of USP12 promoter activity showed that the region spanning −2928 to −1337 bases relative to the transcriptional start site was responsible for the downregulation of USP12 by AKT-mTOR signalling (Supplementary Fig. 1h)."
USP12 affects AKT phosphatase
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USP12 deubiquitinates AKT phosphatase. 1 / 1
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"USP12 deubiquitinates AKT phosphatase PHLPP."
USP12 affects 293 T
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WDR20 binds USP12 and 293 T. 1 / 1
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"We generated YFP-USP12 V279D/F287A and Myc-WDR20 F262A/W306A mutants and confirmed that these mutations largely or completely abrogate WDR20 binding to USP12 in 293 T cells ( Fig. 4 a)."
UBC affects USP12
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No evidence text available
UAF affects USP12
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USP12 binds UAF. 1 / 1
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"A previous report states that USP12 and UAF form a complex with an enzymatic effect, after which the enzymatic effect of USP12 and UAF complex on target protein is stimulated by WDR20 [37,38]."
Tobacco Smoke Pollution increases the amount of USP12. 1 / 1
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No evidence text available
TTR affects USP12
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TTR increases the amount of USP12. 1 / 1
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"In this study, we uncovered that cyclic tension stimulation (CTS) upregulated USP12 expression in hPDLCs and increased expression of USP12 in periodontal tissues in a OTM mouse model."
TRAT1 affects USP12
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No evidence text available
TLR4 affects USP12
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TLR4 activates USP12. 1 / 1
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"In this study we identified that the expression of USP12 is sensitive to TLR4 mediated signalling and USP12 functions to selectively regulate LPS induced pro-inflammatory responses of macrophages."
TCR affects USP12
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TCR leads to the phosphorylation of USP12. 1 / 1
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"TCR stimulation leads to phosphorylation and translocation of USP12 from the nucleus to the cytosol."
TBK1 affects USP46
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USP12 binds USP46 and TBK1. 1 / 1
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sparser
"In addition, USP12 and USP46 were not associated with TBK1 ( xref )."
T-2 toxin affects USP12
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T-2 toxin decreases the amount of USP12. 1 / 1
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No evidence text available
Small hairpin affects USP12
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Small hairpin inhibits USP12. 1 / 1
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"Small hairpin RNA-mediated silencing of USP12 confirmed the findings in both human and mouse lung cancer cells, as evidenced by ELISA quantification (Supplementary Fig. 2b, c)."
STUB1 affects USP12
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STUB1 activates USP12. 1 / 1
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"XREF_BIBR, XREF_BIBR In addition, other E3 ubiquitin ligases are probably involved in the AR regulation process, such as CHIP XREF_BIBR and SKP2 XREF_BIBR which also promote AR degradation, and Siah2, XREF_BIBR RNF6, XREF_BIBR and USP12 XREF_BIBR, XREF_BIBR which promote deubiquitination and AR activation."
SQSTM1 affects OPTN
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sparser
"We have found an intriguing interaction of Usp12 with p62 and Optn, two key receptors necessary for the selective-autophagic clearance of misfolded proteins, mitochondria, and protein aggregates."
SKP2 affects USP12
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SKP2 activates USP12. 1 / 1
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"XREF_BIBR, XREF_BIBR In addition, other E3 ubiquitin ligases are probably involved in the AR regulation process, such as CHIP XREF_BIBR and SKP2 XREF_BIBR which also promote AR degradation, and Siah2, XREF_BIBR RNF6, XREF_BIBR and USP12 XREF_BIBR, XREF_BIBR which promote deubiquitination and AR activation."
SGO1 affects USP12
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No evidence text available
SES affects USP12
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SES activates USP12. 1 / 1
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sparser
"Somatic copy‐number analyses and epigenetic analyses of 12 cancer cell types revealed that SEs generated by focal amplification could aberrantly activate KLF5 , USP12 , PARD6B , or MYC . xref Another study also revealed that the 350‐2000 kb genomic region, including the MYCN oncogene, was amplified aberrantly in neuroblastoma, resulting in the activation of MYCN expression. xref "
SDF4 affects USP12
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No evidence text available
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No evidence text available
RAF1 affects USP12
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No evidence text available
Protease affects USP12
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eidos
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20 Ubiquitin-specific proteases ( USPs ) constitute the largest family of deubiquitinating enzymes , whose catalytic competency is often modulated by their binding partners through unknown mechanisms ."
PPARA affects USP12
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PPARA decreases the amount of USP12. 1 / 1
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No evidence text available
PNMA2 affects USP12
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No evidence text available
PHLPP2 affects WDR20
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sparser
"Both Usp12 and WDR20 alone were able to interact with both PHLPP (Figure xref ) and PHLPPL (Figure xref )."
PHLPP1.WDR48 affects USP12
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PHLPP1.WDR48 binds USP12. 1 / 1
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"We further confirmed the existence of a specific PHLPP1.WDR48 and USP12 complex in vivo by demonstrating that WDR48 and USP12 but not other WD repeat protein WDR5 co-immunoprecipitated with exogenously expressed PHLPP1 in 293T cells (XREF_FIG D)."
PHLPP1 affects USP12, and WDR48
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sparser
"We confirmed the association of endogenous PHLPP1 with WDR48 and USP12 by immunoprecipitation with PHLPP1 antibody ( xref B )."
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sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
PAX4 affects USP12
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PAX4 decreases the amount of USP12. 1 / 1
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No evidence text available
PARD6B affects USP12
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MYC binds KLF5, USP12, and PARD6B. 1 / 1
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sparser
"These super-enhancer amplifications are associated with over-expression of the MYC oncogene as well as the KLF5 , USP12 and PARD6B genes."
PAIP1 affects USP12
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No evidence text available
OPTN affects SQSTM1, and USP12
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sparser
"We have found an intriguing interaction of Usp12 with p62 and Optn, two key receptors necessary for the selective-autophagic clearance of misfolded proteins, mitochondria, and protein aggregates."
NUP160 affects USP12
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No evidence text available
NR2F2 affects USP12
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NR2F2 decreases the amount of USP12. 1 / 1
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No evidence text available
NOTCH1 affects USP12
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No evidence text available
NMRAL1 affects USP12
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No evidence text available
MYC affects PARD6B
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MYC binds KLF5, USP12, and PARD6B. 1 / 1
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sparser
"These super-enhancer amplifications are associated with over-expression of the MYC oncogene as well as the KLF5 , USP12 and PARD6B genes."
| 1

sparser
"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
MTBMA_c15380 affects PHLPP1, USP12, and WDR48
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sparser
"Interestingly, we observed that PHLPP1 specifically associated with WDR48 and USP12 but not other USPs ( xref C )."
MECP2 affects USP12
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No evidence text available
MDM2 affects USP12
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No evidence text available
LAT affects USP12
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No evidence text available
KLF5 affects USP12
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MYC binds KLF5, USP12, and PARD6B. 1 / 1
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sparser
"These super-enhancer amplifications are associated with over-expression of the MYC oncogene as well as the KLF5 , USP12 and PARD6B genes."
IRAK4 affects USP12
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sparser
"Therefore, targeted regulation the activation of USP12-IRAK4 axis is a potential therapeutic strategy for the LPS-induced sepsis treatment."
ILF3 affects USP12
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No evidence text available
IGDCC4 affects USP12
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No evidence text available
HNRNPH1 affects USP12
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No evidence text available
HNF4A affects USP12
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HNF4A decreases the amount of USP12. 1 / 1
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No evidence text available
H2BC21 affects USP12
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No evidence text available
H2AC20 affects USP12
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1 |

No evidence text available
GRB2 affects USP12
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No evidence text available
GPR12 affects USP12
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sparser
"Three SNPs (SBNO2 rs2024092, CARD9 rs10781499, and rs17085007 between GPR12-USP12) were significantly associated with increased UC risk while NKX2-3 rs4409764 was a significant protective factor."
GEM affects USP12
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sparser
"Escherichia coli DH5ɑ harboring the pGEM-USP12 clone was cultured to prepare recombinant plasmid DNA using a Mini Prep kit (Qiagen, Germany)."
GATD3 affects USP12
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No evidence text available
Flag affects USP12
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sparser
"The transfection of Flag-USP12 was achieved in a dose-dependent manner to identify USP12 as a stabilizer for Bax."
Figure affects USP12
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Figure activates USP12. 1 / 1
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eidos
"Based on our results , we propose a tenable model for USP12 activation by UAF1 and WDR20 ( Figure 7 ) ."
FOXO3 affects USP12
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sparser
"Elevated USP12 interacted with FOXO3, preventing its ubiquitin-mediated degradation, which enhanced FOXO3 binding to the PUMA promoter, leading to upregulation of PUMA."
F219 affects WDR48
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WDR48 binds USP12 and F219. 1 / 1
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"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
ESR1 affects USP12
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ESR1 decreases the amount of USP12. 1 / 1
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No evidence text available
EPO affects USP12
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EPO increases the amount of USP12. 1 / 1
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"In a category of ubiquitinylation (XREF_SUPPLEMENTARY), EPO induced the expression of Usp12 and Fbxw7."
EPHA2 affects USP12
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No evidence text available
EGFP affects USP12
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sparser
"Since EGFP-USP12 was absent from FAs (Fig.  xref ) and the members of the USP12/46-WDRs complex were also undetectable in the integrin adhesome (Horton et al, xref ; Kuo et al, xref ; Schiller et al, xref ), we conclude that the USP12/46-WDRs complex binds Itgb1 on endosomes and not in FAs."
| 1

sparser
"Interestingly, Cbl-b and Itch were isolated among the E3 ligases interacting with USP12."

sparser
"In xref , we visualized the top 50 negatively correlated expression genes, and the top five are presented in the form of scatter plots in xref : AL355075.4 ( r = -0.459), AC087286.1 ( r = - 0.558), AC100800.1 ( r = -0.534), ZBTB20-AS5 ( r = -0.534), and USP12-AS1 ( r = -0.566), all with P -value <0.001."
DMWD affects WDR20
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USP12 binds DMWD and WDR20. 1 / 1
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sparser
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
DMWD affects USP46
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DMWD binds USP12 and USP46. 1 / 1
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sparser
"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
DMWD affects USP12, and WDR20
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USP12 binds DMWD and WDR20. 1 / 1
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sparser
"Altogether, our findings suggest a model whereby mutually exclusive binding of DMWD and WDR20 to USP12 may lead to formation of deubiquitinase complexes with distinct subcellular localization, potentially targeting different substrate repertoires."
DMWD affects USP12, and USP46
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DMWD binds USP12 and USP46. 1 / 1
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sparser
"Experimentally, we first confirmed that DMWD binds both USP12 and USP46 through direct co-immunoprecipitation of epitope-tagged proteins."
DHX8 affects USP12
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No evidence text available
DEHP A2780 cells affects USP12
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DEHP A2780 cells activates USP12. 1 / 1
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eidos
"Our multiplex RT-PCR results showed that USP12 expression was increased by DEHP in A2780 cells , and thus , the above-mentioned findings of its influence on cell cycle progression and proliferation suggest that it may induce POF by influencing oocyte maturation ."
DCAF4 affects USP12
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No evidence text available
Cuprizon affects USP12
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Cuprizon decreases the amount of USP12. 1 / 1
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No evidence text available
CX3CL1 affects USP12
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No evidence text available
CLASP2 affects USP12
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No evidence text available
CD6 affects USP12
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No evidence text available
CCL5 affects USP12
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CCL5 activates USP12. 1 / 1
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"Mechanistically, bioinformatics, mass spectrometry, co-IP, RT-qPCR, and western blot analyses indicated that MPP1 increases CCL5 expression by binding to and promoting USP12."
CCL2 affects USP12
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CCL2 inhibits USP12. 1 / 1
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"Moreover, coexpression of Cxcl1 and Ccl2 efficiently attenuated activation of CD8 and CD4 T cells in tumour cells ectopically expressing USP12, as evidenced by the changes in the frequencies of TNF-α IFN-γ cells in the populations (Fig. 5g)."
CBLB affects USP12
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No evidence text available
CADM1 affects USP12
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CADM1 activates USP12. 1 / 1
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reach
"Further activation is mediated by WDR20 binding, which remodels the catalytic cleft and BL2 to fully activate USP12 for catalysis."

No evidence text available
Ad affects USP12
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sparser
"On the other hand, we transfected USP12 overexpression adenovirus (Ad-USP12) into NRCMs to increase the expression of USP12 ( Fig. 2 E)."
ATXN3 affects PHB2, TXN, UCHL5, USP1, USP10, USP12, and USP14
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sparser
"Other examples of protein complexes retrieved include host cell factor-1, galectin 7, p97, ras GTPase binding proteins 1 and 2, WD-repeat containing protein 48 and WD-repeat containing protein 20, and thioredoxin like protein, which interact with BAP, USP1, ataxin-3, USP10, USP12, and USP14 or UCH-L5 [ xref , xref ], respectively."
APP affects USP12
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No evidence text available
AKT2 affects USP12
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AKT2 decreases the amount of USP12. 1 / 1
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"Consistently, ectopic expression of the myristoylated form of AKT1 (myr-AKT1) significantly repressed USP12 expression in both human and mouse tumour cells (Fig. 1k); knockdown of endogenous AKT1 or AKT2, the two major isoforms of AKT, induced higher levels of USP12 than did the control treatment (Fig. 1l)."
AKT1 affects USP12
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AKT1 decreases the amount of USP12. 1 / 1
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"Consistently, ectopic expression of the myristoylated form of AKT1 (myr-AKT1) significantly repressed USP12 expression in both human and mouse tumour cells (Fig. 1k); knockdown of endogenous AKT1 or AKT2, the two major isoforms of AKT, induced higher levels of USP12 than did the control treatment (Fig. 1l)."
AGT affects USP12
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AGT activates USP12. 1 / 1
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"Upregulation of METTL3 reversed the decrease in myocardial hypertrophy induced by AngII in USP12-silenced NRCMs."

No evidence text available
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No evidence text available
293 T affects WDR20
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WDR20 binds USP12 and 293 T. 1 / 1
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reach
"We generated YFP-USP12 V279D/F287A and Myc-WDR20 F262A/W306A mutants and confirmed that these mutations largely or completely abrogate WDR20 binding to USP12 in 293 T cells ( Fig. 4 a)."
1 |

No evidence text available