USP48 affects HMGA2

| 29 11

USP48 binds HMGA2.

| 6 11

USP48 binds HMGA2. 10 / 17

| 6 11

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"Although we failed to identify a conserved SIM motif in HMGA2, our findings demonstrated that the SUMOylated USP48 could still strongly interact with HMGA2, thereby enhancing the affinity of USP48 for ubiquitin chains and augmenting its DUB activity."

38572092

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"The signaling pathway mediated by the USP48–HMGA2 axis plays a critical role in promoting invasion and metastasis of CRC cells."

38572092

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"To further assess the clinical significance of the USP48-HMGA2 axis and establish their correlation in CRC, we performed IHC staining to examine the expression of these proteins in consecutive sections of tissue microarrays (TMAs) consisting of 90 CRC tissues and 86 adjacent normal tissues."

38572092

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"Furthermore, the interaction between endogenous USP48 and HMGA2 was validated through an in-situ proximity ligation assay (PLA) in DLD1, SW480, and HCT116 cells ( xref G and xref )."

38572092

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"Taken together, these results demonstrate the efficacy of DUB-IN-2 in inhibiting USP48 enzyme activity and antagonizing USP48-HMGA2 signaling during CRC metastasis."

38572092

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"These findings suggest a specific interaction between USP48 and HMGA2, indicating that USP48 directly binds to HMGA2."

38572092

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"We have identified an interaction between USP48 and HMGA2, and our study further investigated the involvement of USP48 in maintaining the stability of HMGA2."

38572092

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"USP48 interacts with HMGA2."

38572092

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"Co-immunoprecipitation (Co-IP) assays were used to investigate the interaction between USP48 and HMGA2 in vivo ."

38572092

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"To investigate the impact of SUMOylation on USP48's enzymatic activity as a deubiquitinating enzyme for HMGA2, we assessed the interaction between HMGA2 and USP48."

38572092

USP48 activates HMGA2.

| 7

USP48 activates HMGA2. 7 / 7

| 7

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"Taken together, these human CRC data strongly support our experimental findings regarding USP48-mediated HMGA2 stabilization (Fig. 8M).4 Discussion."

38572092

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"Conversely, knockdown of USP48 enhances HMGA2 degradation."

38572092

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"We hypothesize that the SUMOylation of USP48 may interact with a non-classically conserved SIM motif (V-V-Q-K) in the HMGA2 protein, or induce conformational changes in USP48 to better accommodate the HMGA2 protein44."

38572092

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"We employed cycloheximide (CHX) to halt protein synthesis and demonstrated that USP48 modulated the stability of HMGA2."

38572092

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"Collectively, these findings suggest that USP48 enhances tumor metastasis largely by regulating HMGA2 in vitro and in vivo.3."

38572092

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"Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis."

38572092

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"Cotransfection of USP48 with HDAC4 or HDAC7 synergistically enhances HMGA2 stability, while cotransfection with SENP5 exhibits a weaker effect (Supporting Information Fig. S6A‒C)."

38572092

USP48 increases the amount of HMGA2.

| 6

USP48 increases the amount of HMGA2. 6 / 6

| 6

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"Our findings indicate that USP48 expression enhances HMGA2 protein expression in a dose-dependent manner (Fig. 2A)."

38572092

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"This study has identified that USP48 directly interacts with HMGA2, and overexpression of USP48 significantly increases the protein expression of HMGA2 while decreasing its ubiquitination."

38572092

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"USP48 promoted the migration and invasion of CRC cells by upregulating HMGA2 expression."

38572092

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"The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis."

38572092

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"Our findings demonstrate that only the expression of USP48-WT led to an increase in HMGA2 levels, while USP48-C98S had no effect on protein abundance (Fig. 2C and D)."

38572092

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"Moreover, the co-expression of USP48 shRNA counteracted the elevated endogenous HMGA2 levels induced by USP48 overexpression in both HEK293T and DLD1 cells (Fig. 2E and Fig. S2C)."

38572092

USP48 deubiquitinates HMGA2.

| 5

USP48 deubiquitinates HMGA2. 4 / 4

| 4

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"Our findings collectively indicate that USP48 specifically regulates the stability of HMGA2 protein, rather than affecting HMGA2 mRNA levels.3.3 USP48 deubiquitinates HMGA2."

38572092

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"In contrast, Spautin-1 did not significantly impact the deubiquitination of HMGA2 by USP48, implying alternative mechanisms for its effect on HMGA2 stability (Fig. 7C)."

38572092

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"Our hypothesis posits that USP48 upregulation leads to deubiquitination and stabilization of HMGA2 protein, thereby impacting CRC cell invasion and metastasis."

38572092

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"Our findings demonstrate that USP48-WT significantly attenuates the ubiquitination of HMGA2, whereas USP48-C98S exerts no effect (Fig. 3A)."

38572092

USP48 leads to the deubiquitination of HMGA2 on histidine. 1 / 1

| 1

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"We examined whether USP48 mediates the deubiquitination of HMGA2 by co-transfecting Myc-HMGA2 and His-ubiquitin into HEK293T cells with either wild-type or C98S mutant USP48."

38572092

USP48 inhibits HMGA2.

| 4

USP48 inhibits HMGA2. 4 / 4

| 4

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reach

"Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2."

38572092

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reach

"The findings suggest that SUMOylation of USP48 significantly enhances its ability to stabilize HMGA2 and promote CRC invasion and metastasis in a HMGA2-dependent manner.3.6 DUB-IN-2 hinders the deubiquitinating activity of USP48 and induces the degradation of HMGA2."

38572092

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reach

"We then demonstrate that inhibition of USP48 by shRNA or its newly discovered inhibitor DUB-IN-2 triggers HMGA2 degradation, thereby inhibiting CRC cell metastasis in vitro and in vivo."

38572092

---

➶

reach

"The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis."

38572092

USP48 ubiquitinates HMGA2.

| 1

USP48 leads to the ubiquitination of HMGA2. 1 / 1

| 1

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"Compared to USP48 WT, the USP48–K258R mutant or cotransfection of USP48 with SENP5 did not significantly reduce HMGA2 ubiquitination (Fig. 6H and I)."

38572092

USP48 affects RELA

5 1 | 17 5

USP48 binds RELA.

5 | 6 5

USP48 binds RELA. 10 / 15

5 | 6 4

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"We found that USP48 cleaved poly-Ub-chains bound to RelA."

35913642

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reach

"Another study on USP48-mediated p65/p50 regulation conducted in retinal pigment epithelial cells unveils that knockdown of USP48 causes destabilization of both cytoplasmic and nuclear p65 and downregulates NF-κB activity despite the interaction between USP48 and p65 (59)."

39507445

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"A candidate target of USP31 could be p65/RelA, since there is a physical interaction between USP31 and p65 as indicated by the immunoprecipitation experiments."

16214042

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"Initial studies found that overexpression of USP48 inhibits NF-κB activity downstream of IKKβ and that USP48 also interacts with p65."

27187478

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"It is however possible, that TNF induced ubiquitination of RelA and/or other yet to be identified inducible PTMs of RelA, USP48 or unknown interaction partners are required to mediate this interaction[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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"Although colocalization does not imply an interaction between proteins, previous data described a direct interaction between USP48 and p65."

36077078

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reach

"USP48 interacts with the transcription factor NF-kappaB, deubiquitinates NF-kappaB subunit p65 and promotes its stability and activation, and up-regulates NF-kappaB target genes known to inhibit synaptogenesis."

37781625

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"Initial studies found that overexpression of USP48 inhibits NF-kappaB activity downstream of IKKbeta and that USP48 also interacts with p65."

27187478

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sparser

"The association of USP48 with RelA is likely strengthened upon RelA ubiquitination."

25486460

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"In this study we report that USP48 interacts physically with RelA in the nucleus."

30628021

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

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"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

USP48 deubiquitinates RELA.

1 | 3

USP48 deubiquitinates RELA. 3 / 4

1 | 3

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"As p65 is also a direct interactor and target of USP48 [17], the CSN complex promotes USP48-mediated deubiquitination of p65 and its stabilization on chromatin."

36077078

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➶

reach

"USP48 interacts with the transcription factor NF-kappaB, deubiquitinates NF-kappaB subunit p65 and promotes its stability and activation, and up-regulates NF-kappaB target genes known to inhibit synaptogenesis."

37781625

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"USP48 deubiquitinates p65 and promotes its activation."

37781625

USP48 activates RELA.

| 4

USP48 activates RELA. 4 / 4

| 4

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"USP48 Overexpression Promotes p65 Nuclear Localization."

36077078

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"Interestingly, overexpressed USP48 promoted RelA nuclear accumulation 30 min after TNF stimulation independent of catalytic site Cys C98."

25486460

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reach

"Another study on USP48-mediated p65/p50 regulation conducted in retinal pigment epithelial cells unveils that knockdown of USP48 causes destabilization of both cytoplasmic and nuclear p65 and downregulates NF-κB activity despite the interaction between USP48 and p65 (59)."

39507445

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reach

"USP48 Downregulation Induces Basal p65 Stabilization."

36077078

USP48 inhibits RELA.

| 3

USP48 inhibits RELA. 3 / 3

| 3

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"Our observations that endogenous p65 level is required for normal synapse formation but USP48 overexpression strikingly inhibits synapse formation in a p65-dependent manner can be explained by USP48-dependent up-regulation of a subset of NF-κB target genes, including proBDNF and Caspase-3."

37781625

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reach

"Another study on USP48-mediated p65/p50 regulation conducted in retinal pigment epithelial cells unveils that knockdown of USP48 causes destabilization of both cytoplasmic and nuclear p65 and downregulates NF-κB activity despite the interaction between USP48 and p65 (59)."

39507445

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"Although USP48 stabilizes NF-κB p65 in HeLa cells via the removal of the K48-linked polyubiquitin chain [158], gene silencing of Usp48 increases nuclear NF-κB p65 protein in cultured retinal pigment epithelial cells without any stimulation [159]."

36834633

USP48 ubiquitinates RELA.

| 1

USP48 leads to the ubiquitination of RELA. 1 / 1

| 1

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➶

reach

"Notably, USP48 inhibits NF-κB activity by regulating RelA deubiquitination to reduce cell inflammation and apoptosis [46, 47]."

38245760

USP48 is modified

| 23 1

USP48 is sumoylated.

| 12

USP48 is sumoylated. 10 / 11

| 11

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➶

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"Our findings demonstrated that HDAC4 and HDAC7 promoted the SUMOylation of USP48, while SENP5 cleaved it."

38572092

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➶

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"Although we failed to identify a conserved SIM motif in HMGA2, our findings demonstrated that the SUMOylated USP48 could still strongly interact with HMGA2, thereby enhancing the affinity of USP48 for ubiquitin chains and augmenting its DUB activity."

38572092

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"We hypothesize that the SUMOylation of USP48 may interact with a non-classically conserved SIM motif (V-V-Q-K) in the HMGA2 protein, or induce conformational changes in USP48 to better accommodate the HMGA2 protein xref ."

38572092

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"In CRC cells, it was observed that endogenous USP48 underwent poly-SUMOylation ( xref D and E)."

38572092

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"Co-expression of HDAC4 or HDAC7 facilitated the SUMOylation of USP48 protein ( xref H), while SENP5 inhibited the SUMOylation of USP48 protein ( xref I and J)."

38572092

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"Furthermore, SUMOylation of USP48 significantly enhanced its ability to stabilize HMGA2 and promote CRC cell invasion and metastasis in an HMGA2-dependent manner."

38572092

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"Additionally, substitution of the putative SUMOylation site Lys258 (USP48-K258R) with arginine resulted in a near-complete abrogation of USP48 protein SUMOylation ( xref L)."

38572092

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sparser

"These findings suggest that HDAC4/7 and SENP5 play a role in the dynamic regulation of USP48 protein SUMOylation, with Lys258 identified as a potential site for this modification."

38572092

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"We conducted PLA experiments to determine the subcellular localization of SUMOylated USP48."

38572092

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"Next, we investigated the role of USP48 SUMOylation in driving invasive metastasis in CRC."

38572092

USP48 is sumoylated on lysine. 1 / 1

| 1

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"Our literature review and USP48-interactome mass spectrometry analysis suggest that there may be SUMOylation occurring at a specific lysine residue of the USP48 protein, which could potentially impact its ability to deubiquitinate the HMGA2 protein."

38572092

USP48 is phosphorylated.

| 7 1

USP48 is phosphorylated. 7 / 8

| 7 1

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"USP48 phosphorylation at its C-terminal CK2 phosphorylation sites in response to TNF was confirmed after knockdown of endogenous USP48, followed by reexpression of either siRNA-resistant USP48-FL WT [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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"Exposure to TNFα caused GSK3β-mediated phosphorylation of USP48, leading to deubiquitination of TRAF2 in beas2B cells, increasing JNK signaling upon TNF-α-induction [ xref ]."

31208841

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"The ability of CK2 to phosphorylate USP48 at C-terminal sites was confirmed in kinase assays with recombinant USP48 variants, tagged at the N-term with GST ( Fig. 6 A )."

25486460

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"When USP48-FL was subjected to an in vitro kinase assay prior to and during the labeling reaction, labeling was suppressed indicating that phosphorylation of USP48 in the C-term changes its catalytic [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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"Interestingly, association of CK2 with the CSN and CK2-mediated phosphorylation of its subunits CSN2 and CSN7 have been observed [46] , implying potential reciprocal regulation of CK2 and CSN activit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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"In contrast to HA-Ub-VS-labeling of USP48, which was (transiently) lost after TNF stimulation and upon CK2-mediated phosphorylation ( Fig. 7 A), phosphorylation of USP48 in response to 2 h TNF stimula[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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"In response to TNF however, phosphorylation of USP48 is transient ( Fig. 8 C)."

25486460

USP48 is acetylated.

| 3

USP48 is acetylated. 3 / 3

| 3

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"Moreover, it has been demonstrated that acetylation of USP31 suppresses its activity and plays a protective role in CC cancer cell growth xref ."

35538030

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"To further investigate its activity in tumorigenesis, deacetylase sirtuin 1 (Sirt1) was shown to interact with USP31 by co-immunoprecipitation and blocking the function of Sirt1 by knockdown or the inhibitor nicotinamide could increase the acetylation of USP31."

34184746

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"However, the apoptosis induced by DDP could be resisted by USP31 acetylation in CC xref ."

35983979

USP48 is dephosphorylated.

| 1

USP48 is dephosphorylated. 1 / 1

| 1

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"Thus, dephosphorylation of USP48 and/or its release from RelA and the CSN through an unknown mechanism finally allow efficient polyubiquitination of RelA by ECS SOCS1 , mediating its proteasomal degra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

USP48 affects SIRT6

5 1 | 9 6

USP48 binds SIRT6.

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SIRT6 binds USP48. 6 / 11

5 | 6

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"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

37127248

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"USP48 physically bound and stabilized SIRT6 by K48-linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

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"This dysregulation consequently affects glycolysis through the USP48-SIRT6 axis and contributes to the deterioration of HCC ( xref )."

39229278

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"METTL14 also regulates the glycolytic pathway and inhibits tumor proliferation through the USP48-SIRT6 pathway xref ."

38965238

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"These findings indicate that specifically targeting hepatocyte USP48 or the USP48-SIRT6 axis may be a potential therapeutic strategy for future HCC treatment."

39229278

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"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis."

35798087

USP48 binds SIRT6 and K48. 3 / 3

| 3

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"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis.Lipids include phospholipids, fatty acids, triglycerid[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

35798087

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reach

"USP48 physically bound and stabilized SIRT6 by K48 linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

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➶

reach

"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

37127248

USP48 deubiquitinates SIRT6.

1 | 4

USP48 deubiquitinates SIRT6. 3 / 4

1 | 3

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"The deubiquitination of SIRT6 by USP10 and USP48 inhibits cancer formation by preventing the growth and development of cancer cells."

37175631

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"The elevated USP48 further repress the ubiquitination of sirtuins 6 (SIRT6), therefore mitigating aerobic glycolysis and hindering tumor metastasis in HCC [89]."

38293446

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reach

"METTL14-triggered m6A methylation also inhibits the degradation of ubiquitin specific peptidase 48 (USP48) mRNA, which can deubiquitylate and stabilize sirtuin 6 (SIRT6) to suppresses glycolysis and HCC tumorigenesis."

35974338

USP48 leads to the deubiquitination of SIRT6 on lysine. 1 / 1

| 1

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➶

reach

"USP48 was positively regulated by methyltransferase-like 14 (Mettl14)-induced m A modification and promoted SIRT6 de-ubiquitination at lysine 33 and lysine 128."

37191431

USP48 inhibits SIRT6.

| 1

USP48 inhibits SIRT6. 1 / 1

| 1

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"In human liver cancer, the expression of USP48 is downregulated, reducing the stability of SIRT6, which induces the occurrence of liver cancer."

36578520

USP48 activates SIRT6.

| 1

USP48 activates SIRT6. 1 / 1

| 1

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➶

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"In human liver cancer, the expression of USP48 is downregulated, reducing the stability of SIRT6, which induces the occurrence of liver cancer."

36578520

USP48 affects MDM2

3 | 13 3

USP48 activates MDM2.

| 10

USP48 activates MDM2. 10 / 10

| 10

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"USP48 promotes Mdm2 stability."

28233861

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"To determine whether the observed USP48 mediated Mdm2 upregulation might reflect increased stability on the protein level, we performed a cycloheximide (CHX) chase assay in U2OS cells transfected either with the Mdm2 construct alone or in combination with USP48."

28233861

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"As Mdm2 is best known as a critical negative regulator of p53, in the next set of experiments, we analyzed the impact of the observed USP48 mediated Mdm2 stabilization on cellular p53 protein levels and p53 ubiquitination."

28233861

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"We were surprised to find that USP48 caused Mdm2 stabilization that was not accompanied by a significant decrease in the overall levels of Mdm2 ubiquitination, which was unexpected (XREF_FIG)."

28233861

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"Interestingly, when we analyzed the pattern of Mdm2 ubiquitination in the presence of the deubiquitinase defective mutant USP48 C98S, we again observed that less ubiquitin was attached to Mdm2 via lysine 48 compared to other lysines, suggesting that the deubiquitinase activity of USP48 was not responsible for the previously observed difference and supporting our notion that USP48 did not target Mdm2 with its deubiquitinase activity."

28233861

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"Moreover, these results also suggested that USP48 does not mediate Mdm2 stabilization through the deubiquitination of other Mdm2 regulators."

28233861

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"Nevertheless, we can not exclude the possibility that USP48 (and its deubiquitinase inactive mutants) are capable of recruiting another deubiquitinase responsible for trimming K48 linked ubiquitin, and future studies are necessary to determine the exact mechanism by which USP48 promotes Mdm2 stability."

28233861

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"Recently, USP48 has also been shown to promote the stability of Mdm2 that in turn results in enhanced degradation of p53 42, which has been associated to FA cell death 43."

29891926

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"Moreover, two previously characterized USP48 mutants lacking deubiquitinase activity were also capable of efficiently stabilizing Mdm2, indicating that USP48 utilizes a non canonical, deubiquitination independent mechanism to promote Mdm2 oncoprotein stability."

28233861

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reach

"Notably, USP48 could also promote the stability of oncoprotein mouse double minute 2 (Mdm2) in a deubiquitinylation-independent manner [31]."

35913642

USP48 binds MDM2.

3 | 3

USP48 binds MDM2. 3 / 6

3 | 3

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"One possible explanation could be provided by our finding that USP48 binds to the central acidic domain of Mdm2, a region that was shown by us and others to independently contribute to p53 ubiquitination and to p53 and Mdm2 stability xref xref xref xref xref ."

28233861

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"More detailed subsequent analyses of Mdm2-USP48 interactions suggested the presence of two independent USP48-binding sites in Mdm2 ( xref , xref )."

28233861

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"To test the possible effect of USP48-Mdm2 interactions on Mdm2 protein stability, Mdm2 was expressed in U2OS cells together with increasing amounts of USP48."

28233861

USP48 increases the amount of MDM2.

| 1

USP48 increases the amount of MDM2. 1 / 1

| 1

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"However, if the active trimming of K48 linked ubiquitin was responsible for Mdm2 stabilization, USP48 protein lacking deubiquitinase activity should not be able to modulate Mdm2 protein levels."

28233861

USP48 deubiquitinates MDM2.

| 1

USP48 leads to the deubiquitination of MDM2. 1 / 1

| 1

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reach

"In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels."

28233861

USP48 decreases the amount of MDM2.

| 1

USP48 decreases the amount of MDM2. 1 / 1

| 1

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"In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels."

28233861

USP48 affects GLI1

4 | 6 9

USP48 binds GLI1.

4 | 2 9

USP48 binds GLI1. 10 / 15

4 | 2 9

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"USP48 interacts with Gli1 through its C-terminal DUSP domain to remove ubiquitin moiety from Gli1."

| PMC

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➶

sparser

"USP48 specifically interacts with Gli1 to remove ubiquitin and regulate the Hedgehog signaling pathway, thereby promoting glioblastoma tumorigenesis xref ."

38572092

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"In human glioblastoma, USP48 and Gli1 expression levels were positively correlated, and high USP48 expression levels correlated with higher grades of glioma malignancy [ xref ], suggesting that the USP48-Gli1 regulatory axis is critical for glioma cell proliferation and glioblastoma tumorigenesis."

| PMC

---

➶

sparser

"Additionally, active HH signaling induces USP48 expression via a positive feedback loop by GLI1 binding to the USP48 promoter ( xref )."

37476499

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reach

"Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly."

28623188

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reach

"USP8 prevents SMO ubiquitylation and increases HH signaling activity by promoting SHH-induced cell surface accumulation of SMO (205, 242), whereas USP48 interacts with GLI1 in the nucleus and thereby protects GLI1 from proteasome-dependent degradation."

37476499

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"Zhou and colleagues sustained a positive feedback loop by which HH signaling activates USP48 through the binding of GLI1 to Usp48 promoter."

32531973

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➶

sparser

"This evidence underlies the relevance of USP48-GLI1 regulatory axis for glioma cell proliferation and glioblastoma tumorigenesis [ xref ]."

32531973

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"The deubiquitinase USP48 is able to interact directly with GLI1, cleaving off its ubiquitin and thus enhancing its lifetime. xref In GBM cells, knockdown of USP48 inhibits cell proliferation and expression of GLI1’s downstream targets, leading to repressed tumorigenesis."

29628779

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"Depletion of USP48 inhibits glioma cell viability and tumor generation by partially stabilizing Gli1, which incidates a critical role of the USP48‐Gli1 axis in glioblastoma tumorigenesis ( xref ) ( xref )."

32133826

USP48 activates GLI1.

| 3

USP48 activates GLI1. 3 / 3

| 3

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"Gli1 induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1."

28623188

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➶

reach

"Conversely, the activation of HH signaling induced by the agonist purmorphamine results in an up-regulation of USP37 gene expression, subsequently leading to the stabilization of GLI1 and influencing EMT in breast CSCs.295 Furthermore, Zhou et al discovered that USP48, a deubiquitinase enzyme, activates the Hh signaling pathway by enhancing the stability of the Gli1 protein in glioma cells.296 Through its C-terminal DUSP structural domain, USP48 interacts with Gli1 and removes Ub molecules from it."

40034124

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"In addition to USP7 and OTUB2, the deubiquitinase USP48 was found to activate Hh signaling by stabilizing Gli1 protein in glioma cells [65]."

| PMC

USP48 increases the amount of GLI1.

| 1

USP48 increases the amount of GLI1. 1 / 1

| 1

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"Knockdown of USP48 inhibited the expression of Gli1 target genes and repressed cell proliferation and tumorigenesis [65]."

| PMC

HMGA2 affects USP48

| 7 11

HMGA2 binds USP48.

| 6 11

USP48 binds HMGA2. 10 / 17

| 6 11

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➶

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"Although we failed to identify a conserved SIM motif in HMGA2, our findings demonstrated that the SUMOylated USP48 could still strongly interact with HMGA2, thereby enhancing the affinity of USP48 for ubiquitin chains and augmenting its DUB activity."

38572092

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"The signaling pathway mediated by the USP48–HMGA2 axis plays a critical role in promoting invasion and metastasis of CRC cells."

38572092

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"To further assess the clinical significance of the USP48-HMGA2 axis and establish their correlation in CRC, we performed IHC staining to examine the expression of these proteins in consecutive sections of tissue microarrays (TMAs) consisting of 90 CRC tissues and 86 adjacent normal tissues."

38572092

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"Furthermore, the interaction between endogenous USP48 and HMGA2 was validated through an in-situ proximity ligation assay (PLA) in DLD1, SW480, and HCT116 cells ( xref G and xref )."

38572092

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➶

sparser

"Taken together, these results demonstrate the efficacy of DUB-IN-2 in inhibiting USP48 enzyme activity and antagonizing USP48-HMGA2 signaling during CRC metastasis."

38572092

---

➶

sparser

"These findings suggest a specific interaction between USP48 and HMGA2, indicating that USP48 directly binds to HMGA2."

38572092

---

➶

sparser

"We have identified an interaction between USP48 and HMGA2, and our study further investigated the involvement of USP48 in maintaining the stability of HMGA2."

38572092

---

➶

sparser

"USP48 interacts with HMGA2."

38572092

---

➶

sparser

"Co-immunoprecipitation (Co-IP) assays were used to investigate the interaction between USP48 and HMGA2 in vivo ."

38572092

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reach

"To investigate the impact of SUMOylation on USP48's enzymatic activity as a deubiquitinating enzyme for HMGA2, we assessed the interaction between HMGA2 and USP48."

38572092

HMGA2 activates USP48.

| 1

HMGA2 activates USP48. 1 / 1

| 1

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"Additionally, the depletion of HMGA2 in CRC cells reversed the promoting effect of USP48 on liver and lung metastasis models (Fig. 4M and N)."

38572092

GLI1 affects USP48

4 | 4 10

GLI1 binds USP48.

4 | 2 9

USP48 binds GLI1. 10 / 15

4 | 2 9

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"USP48 interacts with Gli1 through its C-terminal DUSP domain to remove ubiquitin moiety from Gli1."

| PMC

---

➶

sparser

"USP48 specifically interacts with Gli1 to remove ubiquitin and regulate the Hedgehog signaling pathway, thereby promoting glioblastoma tumorigenesis xref ."

38572092

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"In human glioblastoma, USP48 and Gli1 expression levels were positively correlated, and high USP48 expression levels correlated with higher grades of glioma malignancy [ xref ], suggesting that the USP48-Gli1 regulatory axis is critical for glioma cell proliferation and glioblastoma tumorigenesis."

| PMC

---

➶

sparser

"Additionally, active HH signaling induces USP48 expression via a positive feedback loop by GLI1 binding to the USP48 promoter ( xref )."

37476499

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reach

"Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly."

28623188

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reach

"USP8 prevents SMO ubiquitylation and increases HH signaling activity by promoting SHH-induced cell surface accumulation of SMO (205, 242), whereas USP48 interacts with GLI1 in the nucleus and thereby protects GLI1 from proteasome-dependent degradation."

37476499

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"Zhou and colleagues sustained a positive feedback loop by which HH signaling activates USP48 through the binding of GLI1 to Usp48 promoter."

32531973

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sparser

"This evidence underlies the relevance of USP48-GLI1 regulatory axis for glioma cell proliferation and glioblastoma tumorigenesis [ xref ]."

32531973

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"The deubiquitinase USP48 is able to interact directly with GLI1, cleaving off its ubiquitin and thus enhancing its lifetime. xref In GBM cells, knockdown of USP48 inhibits cell proliferation and expression of GLI1’s downstream targets, leading to repressed tumorigenesis."

29628779

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"Depletion of USP48 inhibits glioma cell viability and tumor generation by partially stabilizing Gli1, which incidates a critical role of the USP48‐Gli1 axis in glioblastoma tumorigenesis ( xref ) ( xref )."

32133826

GLI1 activates USP48.

| 2 1

GLI1 activates USP48. 3 / 3

| 2 1

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"The intriguing finding is that Gli1 transcriptionally activates USP48 in glioma cells, thereby establishing a positive feedback loop that governs Hh signaling."

40034124

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reach

"Interestingly, USP48 is transcriptionally activated by Gli1 in glioma cells, thus forms a positive feedback loop to regulate Hh signaling [65]."

| PMC

---

➶

sparser

"Interestingly, USP48 is transcriptionally activated by Gli1 in glioma cells, thus forms a positive feedback loop to regulate Hh signaling [ xref ]."

| PMC

RELA affects USP48

5 | 6 5

USP48 binds RELA. 10 / 15

5 | 6 4

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reach

"We found that USP48 cleaved poly-Ub-chains bound to RelA."

35913642

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reach

"Another study on USP48-mediated p65/p50 regulation conducted in retinal pigment epithelial cells unveils that knockdown of USP48 causes destabilization of both cytoplasmic and nuclear p65 and downregulates NF-κB activity despite the interaction between USP48 and p65 (59)."

39507445

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sparser

"A candidate target of USP31 could be p65/RelA, since there is a physical interaction between USP31 and p65 as indicated by the immunoprecipitation experiments."

16214042

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sparser

"Initial studies found that overexpression of USP48 inhibits NF-κB activity downstream of IKKβ and that USP48 also interacts with p65."

27187478

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reach

"It is however possible, that TNF induced ubiquitination of RelA and/or other yet to be identified inducible PTMs of RelA, USP48 or unknown interaction partners are required to mediate this interaction[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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reach

"Although colocalization does not imply an interaction between proteins, previous data described a direct interaction between USP48 and p65."

36077078

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➶

reach

"USP48 interacts with the transcription factor NF-kappaB, deubiquitinates NF-kappaB subunit p65 and promotes its stability and activation, and up-regulates NF-kappaB target genes known to inhibit synaptogenesis."

37781625

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reach

"Initial studies found that overexpression of USP48 inhibits NF-kappaB activity downstream of IKKbeta and that USP48 also interacts with p65."

27187478

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➶

sparser

"The association of USP48 with RelA is likely strengthened upon RelA ubiquitination."

25486460

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"In this study we report that USP48 interacts physically with RelA in the nucleus."

30628021

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

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sparser

"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

SIRT6 affects USP48

5 | 3 6

SIRT6 binds USP48. 6 / 11

5 | 6

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"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

37127248

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➶

sparser

"USP48 physically bound and stabilized SIRT6 by K48-linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

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➶

sparser

"This dysregulation consequently affects glycolysis through the USP48-SIRT6 axis and contributes to the deterioration of HCC ( xref )."

39229278

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➶

sparser

"METTL14 also regulates the glycolytic pathway and inhibits tumor proliferation through the USP48-SIRT6 pathway xref ."

38965238

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➶

sparser

"These findings indicate that specifically targeting hepatocyte USP48 or the USP48-SIRT6 axis may be a potential therapeutic strategy for future HCC treatment."

39229278

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sparser

"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis."

35798087

USP48 binds SIRT6 and K48. 3 / 3

| 3

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"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis.Lipids include phospholipids, fatty acids, triglycerid[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

35798087

---

➶

reach

"USP48 physically bound and stabilized SIRT6 by K48 linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

---

➶

reach

"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

37127248

USP48 affects apoptotic process

| 13

USP48 activates apoptotic process.

| 10

USP48 activates apoptotic process. 10 / 10

| 10

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"We also investigated the effects of USP48 on H. pylori induced apoptotic cell death in gastric epithelial cells."

35913642

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reach

"After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells."

32359336

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➶

reach

"Furthermore, inhibition of USP48 expression through shRNA knockdown in AML cell lines significantly reduced cell proliferation, promoted apoptosis, and induced G1 phase arrest."

39878157

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➶

reach

"Furthermore, transfection of A20 protein in USP48-depleted cells before H. pylori infection suppressed caspase cleavage and apoptotic cell death (Fig. 4c), indicating that the protective effect on apoptotic cell death is dependent on the expression of A20."

35913642

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reach

"Knockdown of USP48 exacerbated apoptosis induction by H. pylori infection, implying that CSN-associated USP48 supports upregulation of A20 and thereby antagonizes apoptosis of gastric epithelial cells[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37230895

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"Mechanistically, we discovered that caspase-3 recognizes a conserved DEQD motif located at amino acids 611–614 of human USP48 and cleaves USP48 during drug-induced apoptosis."

39878157

---

➶

reach

"USP48 cleavage in drug induced apoptosis of AML."

39878157

---

➶

reach

"All the data indicated that inhibition of USP48 expression could decrease growth of AML cells by inducing apoptosis and G1 phase arrest."

39878157

---

➶

reach

"Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML."

39878157

---

➶

reach

"During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48."

39878157

USP48 inhibits apoptotic process.

| 3

USP48 inhibits apoptotic process. 3 / 3

| 3

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➶

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"USP48 thus enhances the activity of A20 to reduce apoptotic cell death in cells infected with H. pylori."

35913642

---

➶

reach

"Flow cytometry analysis also showed that both HHT and USP48 shRNA induced apoptosis of AML cells, HHT combined with USP48 shRNA enhances cell apoptosis (Figure 6c,d)."

39878157

---

➶

reach

"USP48 knockdown promoted inflammation, oxidative stress, and apoptosis in BAI-treated H O -stimulated KGN cells, indicating that USP48 knockdown abrogated the protective effects of BAI."

38245760

USP48 affects GSDME

3 | 8

USP48 binds GSDME.

3 | 3

USP48 binds GSDME. 1 / 4

3 | 1

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"117 The activation of the NLRP3 inflammasome was found to be regulated by deubiquitinating proteases, but by factors upstream of the inflammasome rather than by the inflammasome itself.118The central mediators of pyroptosis are proteins from the gasdermin family.119 USP48 binds to gasdermin E (GSDME) and deubiquitinates the K48 junction at the K120 and K189 sites to stabilize GSDME, which sensitizes cancer cells to focal death and improves the response to immunotherapy.120 USP22 inhibits the activity of the NLRP3 inflammatory vesicle by promoting ATG5-mediated autophagy, which is the main mechanism to reduce the ubiquitination of the K27 and K48 site junctions and thus stabilize ATG5.121 Few studies investigated the relationship between USP and pyroptosis and the relationship between pyroptosis and BC."

40083330

USP48 binds GSDME and K48. 2 / 2

| 2

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➶

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189 to promote pyroptosis in cancer55."

38572092

---

➶

reach

"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189."

36607699

USP48 activates GSDME.

| 3

USP48 activates GSDME. 3 / 3

| 3

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"USP48 enhanced pyroptosis through stabilizing GSDME."

39075259

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➶

reach

"What’s more, understanding how to regulate GSDME expression has become a current research hotspot, including one research about USP48 promoting cell pyroptosis by stabilizing GSDME [20]."

38853246

---

➶

reach

"USP48 promoted pyroptosis by stabilizing gasdermin E (GSDME)."

36607699

USP48 deubiquitinates GSDME.

| 2

USP48 deubiquitinates GSDME on K189. 1 / 1

| 1

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"Similarly, USP48 can deubiquitinate GSDME at K120 and K189 by removing the K48-linked ubiquitin chains, thereby augmenting cancer cell susceptibility to pyroptosis in response to treatment 118."

37781519

USP48 deubiquitinates GSDME on K120. 1 / 1

| 1

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➶

reach

"Similarly, USP48 can deubiquitinate GSDME at K120 and K189 by removing the K48-linked ubiquitin chains, thereby augmenting cancer cell susceptibility to pyroptosis in response to treatment 118."

37781519

USP48 affects pyroptosis

| 1 9

USP48 activates pyroptosis. 10 / 10

| 1 9

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"USP48 promotes pyroptosis in cancer cells by removing K48-linked ubiquitination at positions K120 and K189 of the GSDME [21]."

38245760

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➶

reach

"It was found that deletion of USP48 significantly inhibited tumor cell pyroptosis."

40201182

---

➶

reach

"USP48 stabilized GSDME to promote pyroptosis by removing K48-linked ubiquitination at K120 and K189 on GSDME (23)."

40201182

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➶

reach

"A CRISPR-Cas9 screen identified that loss of USP48, a deubiquitinating enzyme, significantly inhibited cell pyroptosis."

36607699

---

➶

reach

"USP48 promoted pyroptosis by stabilizing gasdermin E (GSDME)."

36607699

---

➶

eidos

"USP48 promoted pyroptosis by stabilizing gasdermin E ( GSDME ) ."

36607699

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reach

"USP48 is implicated in activation of NF-κB (Mirra et al. 2022; Schweitzer and Naumann 2015; Ghanem et al. 2019), induces pyroptosis by stabilization of Gasdermin E (Ren et al. 2023) and promotes cell survival in Helicobacter pylori infection (Jantaree et al. 2022)."

39985644

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➶

reach

"A CRISPR-Cas9 screen approach for identifying regulators of pyroptosis in cancer revealed that loss of USP48, a deubiquitinating enzyme, remarkably suppressed cell pyroptosis."

39075259

---

➶

reach

"USP48 enhanced pyroptosis through stabilizing GSDME."

39075259

---

➶

reach

"What’s more, understanding how to regulate GSDME expression has become a current research hotspot, including one research about USP48 promoting cell pyroptosis by stabilizing GSDME [20]."

38853246

USP48 affects ARL3

| 5 4

USP48 binds ARL3.

| 4 4

USP48 binds ARL3. 8 / 8

| 4 4

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"These results were consistent and independent of the epitope tag used (Figure S4), overall suggesting that the USP48 interaction and stabilisation of ARL3 and UNC119a occur by different mechanisms.In order to dissect which USP48 domain was involved in the interaction, we performed co-immunoprecipitation experiments with either ARL3 or UNC119a and several USP48 proteins carrying different domain deletions."

36293380

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"USP48 Interacts with ARL3 and UNC119a."

36293380

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"To study whether the interaction between USP48 and ARL3 and UNC119a was dependent on the USP48 DUB activity, the protein stability of these interactors was assayed in different conditions, and several USP48-derived constructs (USP48 WT , catalytically inactive USP48 C98S or hyperactive USP48 S886−888D )."

36293380

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"ARL3 co-immunoprecipitated with all USP48-derived proteins, indicating that the interaction between USP48 and ARL3 most probably occurs via the UCH catalytic domain of USP48 ( xref A)."

36293380

---

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reach

"To study whether the interaction between USP48 and ARL3 and UNC119a was dependent on the USP48 DUB activity, the protein stability of these interactors was assayed in different conditions, and several USP48-derived constructs (USP48 , catalytically inactive USP48 or hyperactive USP48 )."

36293380

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➶

reach

"ARL3 co-immunoprecipitated with all USP48-derived proteins, indicating that the interaction between USP48 and ARL3 most probably occurs via the UCH catalytic domain of USP48 (Figure 7A)."

36293380

---

➶

reach

"This result suggested that the CK2 domain, and to a minor extent the UBL domain, were crucial for the interaction between UNC119a and USP48.In summary, all our data support that USP48 can interact with and stabilise ARL3 and UNC119a using different mechanisms and distinct protein domains."

36293380

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"USP48 also interacts with IRD-associated proteins ARL3 and UNC119a and stabilizes their protein levels using different mechanisms, indicating its importance in intracellular protein transport and ciliary trafficking to the photoreceptor outer segment."

37047708

USP48 activates ARL3.

| 1

USP48 activates ARL3. 1 / 1

| 1

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"In agreement with the observed localisation of USP48 at synaptic sites [36] and plexiform layers in our immunostained retinal cryosections, USP48 might also be modulating the functions of UNC119a and ARL3, not only in the OS and cilium but in synapses too.Finally, over the past few years, there has been a growing interest in the development of small-molecule DUB inhibitors as therapeutic agents, mainly to treat cancer [66]."

36293380

USP48 affects TRAF2

3 | 2 3

USP48 binds TRAF2.

3 | 3

TRAF2 binds USP48. 3 / 6

3 | 3

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"To confirm that the interaction between TRAF2 and USP31 in mammalian cells occurs via the RING finger domain of TRAF2, as indicated by our two-hybrid results, a mutated form of TRAF2 with a RING finge[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16214042

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"Co-immunoprecipitation experiments indicated that USP31 does not interact with a mutated TRAF2 that lacks the RING finger domain (C)."

16214042

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sparser

"These results show that USP31 and TRAF2 interact specifically in mammalian cells and their interaction requires an intact RING finger domain of TRAF2 and the amino terminal 483 residues of USP31."

16214042

USP48 decreases the amount of TRAF2.

| 1

USP48 decreases the amount of TRAF2. 1 / 1

| 1

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➶

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"Down-regulation of USP48 increases K48 linked polyubiquitination of TRAF2 and reduces TRAF2 protein levels."

28874458

USP48 activates TRAF2.

| 1

USP48 activates TRAF2. 1 / 1

| 1

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➶

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"A noteworthy fact is that TRAF2 in JNK pathway was targeted by USP48, but not TRAF2 in NF-kappaB signaling [XREF_BIBR]."

31208841

USP48 affects NFkappaB

| 5 3

USP48 activates NFkappaB.

| 2 2

USP48 activates NFkappaB. 3 / 3

| 1 2

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"For example, USP6/TRE17 is involved in activation of NF-κB pathway [ 24 , 25 ]; USP8 regulates T cell homeostasis and mitophagy in mitochondria [ 26 , 27 ]; USP10 or USP42 regulates p53 localization a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

32561457

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"However, subsequent studies demonstrated that in fact USP48 promotes NF-kappaB activity by co-operating with the COP9 signalosome to trim K48 linked polyubiquitin chains from p65 in the nucleus [XREF_BIBR]."

27187478

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"The inhibition of NF-κB activation by USP31 was not due to a reduction of effector protein expression, since Western blot analysis revealed that the levels of all effector proteins were unaffected by [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16214042

USP48 bound to RELA activates NFkappaB. 1 / 1

| 1

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➶

reach

"USP48 interacts with the transcription factor NF-kappaB, deubiquitinates NF-kappaB subunit p65 and promotes its stability and activation, and up-regulates NF-kappaB target genes known to inhibit synaptogenesis."

37781625

USP48 inhibits NFkappaB.

| 2

USP48 inhibits NFkappaB. 2 / 2

| 2

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➶

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"Depletion of USP48 decreases NF-kappaB target gene expression [XREF_BIBR]."

28881649

---

➶

reach

"Initial studies found that overexpression of USP48 inhibits NF-kappaB activity downstream of IKKbeta and that USP48 also interacts with p65."

27187478

USP48 deubiquitinates NFkappaB.

| 1

USP48 deubiquitinates NFkappaB. 1 / 1

| 1

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➶

reach

"USP48 interacts with the transcription factor NF-kappaB, deubiquitinates NF-kappaB subunit p65 and promotes its stability and activation, and up-regulates NF-kappaB target genes known to inhibit synaptogenesis."

37781625

USP48 binds NFkappaB.

| 1

USP48 binds NFkappaB. 1 / 1

| 1

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➶

sparser

"USP48 interacts with the transcription factor NF-κB, deubiquitinates NF-κB subunit p65 and promotes its stability and activation, and up-regulates NF-κB target genes known to inhibit synaptogenesis."

37781625

METTL14 affects USP48

| 1 7

METTL14 activates USP48.

| 1 3

METTL14 activates USP48. 4 / 4

| 1 3

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➶

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"For instance, it has been shown that methyltransferase 14, N -adenosine-methyltransferase subunit (METTL14) upregulates ubiquitin specific peptidase 48 to alleviate liver cancer by regulating Sirtuin 6 stability (4)."

38426536

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➶

eidos

"USP48 is upregulated by Mettl14 to attenuate hepatocellular carcinoma via regulating SIRT6 stabilization ."

33903120

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➶

reach

"USP48 is upregulated by Mettl14 to attenuate hepatocellular carcinoma via regulating SIRT6 stabilization."

33903120

---

➶

reach

"It has been demonstrated that methyltransferase-like 14-induced m6A modification participates in the regulation of USP48 in hepatocellular carcinoma by maintaining Usp48 mRNA stability (43)."

37205094

METTL14 increases the amount of USP48.

| 2

METTL14 increases the amount of USP48. 2 / 2

| 2

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➶

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"Furthermore, studies show that METTL14 could enhance the ubiquitin-specific protease 48 (USP48) level through the maintenance of USP48 mRNA stability."

38293446

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➶

reach

"Du et al. [ 69 ] found that METTL14-induced m6A modification regulated the expression of ubiquitin-specific peptidase 48 (USP48) by maintaining its mRNA stability."

35798087

METTL14 inhibits USP48.

| 1

METTL14 inhibits USP48. 1 / 1

| 1

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➶

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"In contrast, METTL14 inhibits HCC growth by upregulating USP48, HNF3γ, and miR126, while silencing SLC7A11."

40302799

METTL14 demethylates USP48.

| 1

METTL14 leads to the demethylation of USP48. 1 / 1

| 1

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➶

reach

"METTL14-triggered m6A methylation also inhibits the degradation of ubiquitin specific peptidase 48 (USP48) mRNA, which can deubiquitylate and stabilize sirtuin 6 (SIRT6) to suppresses glycolysis and HCC tumorigenesis."

35974338

ARL3 affects USP48

| 4 4

USP48 binds ARL3. 8 / 8

| 4 4

---

➶

reach

"These results were consistent and independent of the epitope tag used (Figure S4), overall suggesting that the USP48 interaction and stabilisation of ARL3 and UNC119a occur by different mechanisms.In order to dissect which USP48 domain was involved in the interaction, we performed co-immunoprecipitation experiments with either ARL3 or UNC119a and several USP48 proteins carrying different domain deletions."

36293380

---

➶

sparser

"USP48 Interacts with ARL3 and UNC119a."

36293380

---

➶

sparser

"To study whether the interaction between USP48 and ARL3 and UNC119a was dependent on the USP48 DUB activity, the protein stability of these interactors was assayed in different conditions, and several USP48-derived constructs (USP48 WT , catalytically inactive USP48 C98S or hyperactive USP48 S886−888D )."

36293380

---

➶

sparser

"ARL3 co-immunoprecipitated with all USP48-derived proteins, indicating that the interaction between USP48 and ARL3 most probably occurs via the UCH catalytic domain of USP48 ( xref A)."

36293380

---

➶

reach

"To study whether the interaction between USP48 and ARL3 and UNC119a was dependent on the USP48 DUB activity, the protein stability of these interactors was assayed in different conditions, and several USP48-derived constructs (USP48 , catalytically inactive USP48 or hyperactive USP48 )."

36293380

---

➶

reach

"ARL3 co-immunoprecipitated with all USP48-derived proteins, indicating that the interaction between USP48 and ARL3 most probably occurs via the UCH catalytic domain of USP48 (Figure 7A)."

36293380

---

➶

reach

"This result suggested that the CK2 domain, and to a minor extent the UBL domain, were crucial for the interaction between UNC119a and USP48.In summary, all our data support that USP48 can interact with and stabilise ARL3 and UNC119a using different mechanisms and distinct protein domains."

36293380

---

➶

sparser

"USP48 also interacts with IRD-associated proteins ARL3 and UNC119a and stabilizes their protein levels using different mechanisms, indicating its importance in intracellular protein transport and ciliary trafficking to the photoreceptor outer segment."

37047708

USP48 affects RUNX1

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RUNX1 binds USP48. 7 / 7

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"To verify whether the two proteins interact with each other, through co-IP, and the results show that RUNX1 can bind to USP31 (Fig.  xref D)."

38886545

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"As RUNX1 can bind to USP31, to further investigate the interaction by searching for inhibitors against both by Genomics of Drug Sensitibity in Cancer (GDSC)."

38886545

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"The docking results with the lowest binding energy are shown in Fig.  xref B. Therefore, we selected MP470 for interfering with the interaction between RUNX1 and USP31."

38886545

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"The results showed that MP470 increased the ubiquitination level of RUNX1, leading to a decrease in RUNX1 protein level, which may be due to its inhibition of the interaction between RUNX1 and USP31."

38886545

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"Taken together, these data further supported that the binding of USP31 to RUNX1, and showed that USP31 could mediate the deubiquitination of RUNX1 and regulate its transcriptional function."

38886545

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"In addition, there may be an interaction between the two proteins, RUNX1 and USP31, with modification of deubiquitination leading to upregulation of RUNX1 level expression (Fig.  xref )."

38886545

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"MP470 was chosen as an inhibitor of the interaction between USP31 and RUNX1, results suggested that the USP31 protein acts through deubiquitination to affect the RUNX1 protein."

38886545

USP48 affects POMC

| 5 2

USP48 activates POMC.

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USP48 activates POMC. 5 / 5

| 3 2

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"Different from BRAF V600E, USP48 mutation-mediated transcriptional activation of POMC appears not be linked to the activation of Erk1/2 or its downstream signaling cascade."

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"Herein we show that Gli1 is pivotal for USP48 action on CRH-induced ACTH synthesis and suggest that the USP48 mutants decrease Gli1 ubiquitination that in turn stabilizes and amplifies the stimulatory action of CRH on ACTH synthesis.It is notable that both deubiquitinases mutated in corticotroph tumors, USP8 and USP48, have among their targets members of the SHH pathway: Smoothened and Gli1, respectively."

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"In contrast, we provide the evidence to demonstrate that the NF-κB pathway is involved in USP48 -mediated transcriptional activation of POMC ."

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"Mutations in the deubiquitinating enzymes USP8 and USP48 have been shown to promote the development of ACTH PitNETs, suggesting that these enzymes play a crucial role in the pathogenesis of the disease [10, 11]."

39910602

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"In contrast, we provide the evidence to demonstrate that the NF-κB pathway is involved in USP48-mediated transcriptional activation of POMC."

30093687

Mutated USP48 activates POMC. 1 / 1

| 1

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"Different from BRAF V600E, USP48 mutation-mediated transcriptional activation of POMC appears not be linked to the activation of Erk1/2 or its downstream signaling cascade."

30093687

USP48 increases the amount of POMC.

| 1

Mutated USP48 increases the amount of POMC. 1 / 1

| 1

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"In agreement with these findings, USP48 mutations induced hyper-release of ACTH, which resulted in increased expression of the POMC gene in AtT cells after stimulation with corticotrophin-releasing hormone [237]."

36834633

RUNX1 affects USP48

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RUNX1 binds USP48. 7 / 7

| 7

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"To verify whether the two proteins interact with each other, through co-IP, and the results show that RUNX1 can bind to USP31 (Fig.  xref D)."

38886545

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sparser

"As RUNX1 can bind to USP31, to further investigate the interaction by searching for inhibitors against both by Genomics of Drug Sensitibity in Cancer (GDSC)."

38886545

---

➶

sparser

"The docking results with the lowest binding energy are shown in Fig.  xref B. Therefore, we selected MP470 for interfering with the interaction between RUNX1 and USP31."

38886545

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➶

sparser

"The results showed that MP470 increased the ubiquitination level of RUNX1, leading to a decrease in RUNX1 protein level, which may be due to its inhibition of the interaction between RUNX1 and USP31."

38886545

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➶

sparser

"Taken together, these data further supported that the binding of USP31 to RUNX1, and showed that USP31 could mediate the deubiquitination of RUNX1 and regulate its transcriptional function."

38886545

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sparser

"In addition, there may be an interaction between the two proteins, RUNX1 and USP31, with modification of deubiquitination leading to upregulation of RUNX1 level expression (Fig.  xref )."

38886545

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"MP470 was chosen as an inhibitor of the interaction between USP31 and RUNX1, results suggested that the USP31 protein acts through deubiquitination to affect the RUNX1 protein."

38886545

CK2 affects USP48

| 2 5

CK2 phosphorylates USP48.

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CK2 phosphorylates USP48. 6 / 6

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"Phosphorylation of USP48 at its C-terminal CK2 consensus sites was evidenced in in vitro phosphorylation assays with recombinant CK2 and epitope-tagged USP48 variants, which, after overexpression, had[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"In support of a functional role of CK2 in the regulation of USP48 catalytic activity, phosphorylation of USP48 at CK2 consensus sites as well as co-IP of CK2α and CSN (CSN3) were observed 2 h after TN[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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"These results indicate that CK2-mediated phosphorylation of USP48 at its C-terminal CK2 consensus sites and its binding to K48-linked Ub-chains ( Fig. 5 H), both of which promote USP48 Ub-chain-trimmi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We demonstrate that (I) USP48 preferentially trims long (K48-linked) Ub-chains, an as yet unique property within the USP family, (II) CK2 phosphorylates USP48 at C-terminal CK2 consensus sites, thereb[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"CK2-mediated phosphorylation of USP48 at C-terminal CK2 consensus sites, in vitro and in response to TNF, enhances its Ub-chain-trimming activity ( Fig. 8 A–C)."

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"The ability of CK2 to phosphorylate USP48 at C-terminal sites was confirmed in kinase assays with recombinant USP48 variants, tagged at the N-term with GST."

25486460

CK2 activates USP48.

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CK2 activates USP48. 1 / 1

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"It also contains a regulatory CK2 domain—where three serines can be phosphorylated by the CK2 kinase, thus enhancing USP48 deubiquitinating function–as well as a ubiquitin-like (UBL) domain, which also contains a nuclear localization signal (NLS) [16,17]."

36077078

USP48 affects cell population proliferation

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USP48 activates cell population proliferation.

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USP48 activates cell population proliferation. 5 / 5

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"In vivo and in vitro functional investigations have demonstrated that overexpression of USP48 promotes the proliferation of CRC cells."

38572092

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"XREF_BIBR In GBM cells, knockdown of USP48 inhibits cell proliferation and expression of GLI1 's downstream targets, leading to repressed tumorigenesis."

29628779

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"MTT experiments showed that both HHT and USP48 shRNA could inhibit AML cell proliferation, and inhibiting USP48 could enhance the effect of HHT (Figure 6b)."

39878157

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"Suppression of USP48 inhibits proliferation and promotes tumor cell death, making it a potential target for cancer therapy.PR-619, a broad DUB inhibitor that includes USP48, is considered a promising anti-cancer drug."

39878157

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"Furthermore, inhibition of USP48 expression through shRNA knockdown in AML cell lines significantly reduced cell proliferation, promoted apoptosis, and induced G1 phase arrest."

39878157

USP48 inhibits cell population proliferation.

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USP48 inhibits cell population proliferation. 1 / 1

| 1

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"Knockdown of USP48 leads to the inhibition of Gli1 target gene expression, thereby suppressing cell proliferation and tumorigenesis."

40034124

USP48 affects Neoplasm Metastasis

| 1 5

USP48 activates Neoplasm Metastasis.

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"Consequently, we proceeded to investigate the function of USP48 in promoting CRC metastasis in vivo.Our findings consistently demonstrate that knockdown of USP48 in CRC cells significantly suppresses tumor metastasis compared to control cells in liver and lung metastasis models of CRC."

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"Collectively, these findings suggest that USP48 enhances tumor metastasis largely by regulating HMGA2 in vitro and in vivo.3."

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"Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis."

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"Subsequent research revealed that USP48 promotes tumor progression, metastasis, and chemoresistance by inhibiting the degradation of cancer-related proteins such as MDM2, RelA, Gli1, Aurora B, and HMGA2."

39878157

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"Interestingly, we found that reconstitution of USP48 WT in endogenous USP48-deficient DLD1 cells significantly increased cell migration capacity as well as lung metastasis compared to the USP48 K258R mutant (Fig. 6L and M)."

38572092

USP48 inhibits Neoplasm Metastasis.

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USP48 inhibits Neoplasm Metastasis. 1 / 1

| 1

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"The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP , and alleviates the metastasis in vivo ."

32359336

USP48 affects CTNNB1

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USP48 ubiquitinates CTNNB1.

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USP48 leads to the ubiquitination of CTNNB1. 2 / 2

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"For example, the oncogenic miR-489-3p mediates the inhibition of β-catenin ubiquitination by ubiquitin specific peptidase 48 (USP48), inducing malignant phenotypes such as growth, migration, and EMT in NSCLC cells [104]."

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"For example, the oncogenic miR-489-3p mediates the inhibition of β-catenin ubiquitination by ubiquitin specific peptidase 48 (USP48), inducing malignant phenotypes such as growth, migration, and EMT in NSCLC cells [ xref ]."

40087753

USP48 binds CTNNB1.

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USP48 binds CTNNB1. 2 / 2

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"Afterwards, Co-IP assay was performed to detect the interaction between USP48 and β-catenin proteins."

35413838

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"Afterwards, Co-IP, RNA pulldown, and luciferase reporter assays verified the interaction of USP48 with β-catenin."

35413838

USP48 inhibits CTNNB1.

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USP48 inhibits CTNNB1. 1 / 1

| 1

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"Additionally , miR-489-3p inactivates Wnt / beta-catenin signaling pathway and regulates USP48 to inhibit the ubiquitination of beta-catenin ."

35413838

USP48 deubiquitinates CTNNB1.

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USP48 leads to the deubiquitination of CTNNB1. 1 / 1

| 1

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"For example, the oncogenic miR-489-3p mediates the inhibition of β-catenin ubiquitination by ubiquitin specific peptidase 48 (USP48), inducing malignant phenotypes such as growth, migration, and EMT in NSCLC cells [104]."

40087753

USP48 affects BRCA1

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USP48 inhibits BRCA1.

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USP48 inhibits BRCA1. 4 / 4

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"USP48 loss enhances BRCA1 and RAD51 localization in FA cells."

29891926

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"Moreover, both the increased GC and SSA repair seen in USP48 depleted cells required BRCA1, as well as CtIP."

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"In cells we reveal that USP48 antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48 results in positioning 53BP1 further from the break site and in extended resection lengths."

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"Interestingly , in the absence of USP48 , single-stranded annealing is promoted , which is likely due to the increased resection that occurs if BRCA1 is not properly constrained by USP48 ."

31164001

USP48 activates BRCA1.

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USP48 activates BRCA1. 2 / 2

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"Thus, high levels or activity of USP48 would be expected to decrease resection lengths and thus reduce GC, and phenocopy aspects of BRCA1 loss."

29335415

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"We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function."

29335415

TRAF2 affects USP48

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TRAF2 binds USP48. 3 / 6

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"To confirm that the interaction between TRAF2 and USP31 in mammalian cells occurs via the RING finger domain of TRAF2, as indicated by our two-hybrid results, a mutated form of TRAF2 with a RING finge[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16214042

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"Co-immunoprecipitation experiments indicated that USP31 does not interact with a mutated TRAF2 that lacks the RING finger domain (C)."

16214042

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"These results show that USP31 and TRAF2 interact specifically in mammalian cells and their interaction requires an intact RING finger domain of TRAF2 and the amino terminal 483 residues of USP31."

16214042

MDM2 affects USP48

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USP48 binds MDM2. 3 / 6

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"One possible explanation could be provided by our finding that USP48 binds to the central acidic domain of Mdm2, a region that was shown by us and others to independently contribute to p53 ubiquitination and to p53 and Mdm2 stability xref xref xref xref xref ."

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"More detailed subsequent analyses of Mdm2-USP48 interactions suggested the presence of two independent USP48-binding sites in Mdm2 ( xref , xref )."

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"To test the possible effect of USP48-Mdm2 interactions on Mdm2 protein stability, Mdm2 was expressed in U2OS cells together with increasing amounts of USP48."

28233861

GSDME affects USP48

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"117 The activation of the NLRP3 inflammasome was found to be regulated by deubiquitinating proteases, but by factors upstream of the inflammasome rather than by the inflammasome itself.118The central mediators of pyroptosis are proteins from the gasdermin family.119 USP48 binds to gasdermin E (GSDME) and deubiquitinates the K48 junction at the K120 and K189 sites to stabilize GSDME, which sensitizes cancer cells to focal death and improves the response to immunotherapy.120 USP22 inhibits the activity of the NLRP3 inflammatory vesicle by promoting ATG5-mediated autophagy, which is the main mechanism to reduce the ubiquitination of the K27 and K48 site junctions and thus stabilize ATG5.121 Few studies investigated the relationship between USP and pyroptosis and the relationship between pyroptosis and BC."

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USP48 binds GSDME and K48. 2 / 2

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189 to promote pyroptosis in cancer55."

38572092

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189."

36607699

USP48 affects homologous recombination

| 5

USP48 inhibits homologous recombination.

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USP48 inhibits homologous recombination. 4 / 4

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"Together, the findings indicate that USP48 antagonizes BRCA1/BARD1 Ub ligase-dependent activities in HR, creating a balance that regulates DNA end-resection tract length [78, 80] (Figure 5B)."

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"As we had found that USP48 loss enhances HR in DeltaFANCC cells, we determined whether it could also alleviate chromosome breaks in DeltaFANCC cells."

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"By contrast, USP48 depletion did not enhance MMC induced RAD51 focus formation in control cells, suggesting that USP48 may inhibit HR processes specifically in an FA deficient background."

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"At 18h after MMC treatment, recruitment of RAD51 into foci was significantly higher in U2OS cells simultaneously depleted for both FANCC and USP48 by siRNA treatment, compared to cells depleted for FANCC alone, implying that USP48 loss restores HR efficiency at replication forks encountering ICL damage in FA deficient cells."

29891926

USP48 activates homologous recombination.

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USP48 activates homologous recombination. 1 / 1

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"BRCC36, USP13, USP26, USP37 and USP48 all participate in regulating BRCA1-mediated HR, but they seemly have little effect on the stability of BRCA1 ."

38734703

USP48 affects Neoplasms

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USP48 activates Neoplasms. 5 / 5

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"Finally, overexpression of USP48 enhanced the therapeutic efficacy of PD-1 inhibitors in tumors in mouse models."

36607699

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"Consequently, we proceeded to investigate the function of USP48 in promoting CRC metastasis in vivo.Our findings consistently demonstrate that knockdown of USP48 in CRC cells significantly suppresses tumor metastasis compared to control cells in liver and lung metastasis models of CRC."

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"It is therefore of interest to show that somatic activating pathogenic variants in the USP48 gene may induce corticotroph tumorigenesis by enhancing corticotroph tumor response to hypothalamic CRH stimulation.Among the potential USP48 substrates, Gli1 is of particular interest for corticotroph pathophysiology."

31222332

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"Collectively, these findings suggest that USP48 enhances tumor metastasis largely by regulating HMGA2 in vitro and in vivo.3."

38572092

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"Subsequent research revealed that USP48 promotes tumor progression, metastasis, and chemoresistance by inhibiting the degradation of cancer-related proteins such as MDM2, RelA, Gli1, Aurora B, and HMGA2."

39878157

USP48 affects K48

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USP48 binds SIRT6 and K48. 3 / 3

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"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis.Lipids include phospholipids, fatty acids, triglycerid[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

35798087

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"USP48 physically bound and stabilized SIRT6 by K48 linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

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"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

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USP48 binds GSDME and K48. 2 / 2

| 2

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189 to promote pyroptosis in cancer55."

38572092

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189."

36607699

USP48 affects Cell Survival

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USP48 activates Cell Survival. 5 / 5

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"USP48 is implicated in activation of NF-κB (Mirra et al. 2022; Schweitzer and Naumann 2015; Ghanem et al. 2019), induces pyroptosis by stabilization of Gasdermin E (Ren et al. 2023) and promotes cell survival in Helicobacter pylori infection (Jantaree et al. 2022)."

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"Together, USP48 and A20 promoted GC cell survival during H. pylori infection and suggested an oncogenic role for A20."

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"USP48 and A20 synergistically promote cell survival in Helicobacter pylori infection."

35913642

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"Furthermore, USP48 promotes cell survival during H. pylori infection through A20-dependent suppression of caspases activity and apoptotic cell death."

35913642

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"Further, USP48 promotes cell survival and antagonizes also other E3 ligase functions which are involved in genome stability and DNA repair."

30628021

K48 affects USP48

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USP48 binds SIRT6 and K48. 3 / 3

| 3

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"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis.Lipids include phospholipids, fatty acids, triglycerid[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

35798087

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"USP48 physically bound and stabilized SIRT6 by K48 linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

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"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

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USP48 binds GSDME and K48. 2 / 2

| 2

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189 to promote pyroptosis in cancer55."

38572092

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189."

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Csn affects USP48

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Csn binds USP48. 4 / 4

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"In this way, we identified CSN1 as the CSN subunit that interacts with USP48 (Fig.  xref e)."

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"USP48 and the CSN constitutively interact in the nucleus."

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"Co-IPs between human purified CSN, recombinant RelA and recombinant full length USP48 (USP48-FL) revealed direct interactions between CSN and USP48 ( Fig. 3 D) and between CSN and RelA ( Fig. 3 E) but[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"An intriguing example presented by Michael Naumann (Germany) is USP48, directly interacting with CSN in the nucleus, regulates the turnover of active NF-κB/RelA."

28837155

USP48 affects USP48

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USP48 activates USP48. 4 / 4

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"The findings suggest that SUMOylation of USP48 significantly enhances its ability to stabilize HMGA2 and promote CRC invasion and metastasis in a HMGA2-dependent manner.3.6 DUB-IN-2 hinders the deubiquitinating activity of USP48 and induces the degradation of HMGA2."

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"We hypothesize that the SUMOylation of USP48 may interact with a non-classically conserved SIM motif (V-V-Q-K) in the HMGA2 protein, or induce conformational changes in USP48 to better accommodate the HMGA2 protein44."

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"These results indicate that CK2 mediated phosphorylation of USP48 at its C-terminal CK2 consensus sites and its binding to K48 linked Ub-chains, both of which promote USP48 Ub-chain-trimming activity,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

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"In response to TNF-alpha, serine phosphorylation of USP48 by GSK3beta increases USP48 activity."

33466790

USP48 affects UNC119a

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USP48 binds UNC119a. 4 / 4

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"This result suggested that the CK2 domain, and to a minor extent the UBL domain, were crucial for the interaction between UNC119a and USP48.In summary, all our data support that USP48 can interact with and stabilise ARL3 and UNC119a using different mechanisms and distinct protein domains."

36293380

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"Alternatively, the DUB-independent regulation of UNC119a levels by USP48 could be hinting at an indirect interaction between UNC119a and USP48, through a third partner or via the formation of a stabilising complex with USP48, resulting in the stabilisation of UNC119a."

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"To study whether the interaction between USP48 and ARL3 and UNC119a was dependent on the USP48 DUB activity, the protein stability of these interactors was assayed in different conditions, and several USP48-derived constructs (USP48 , catalytically inactive USP48 or hyperactive USP48 )."

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"These results were consistent and independent of the epitope tag used (Figure S4), overall suggesting that the USP48 interaction and stabilisation of ARL3 and UNC119a occur by different mechanisms.In order to dissect which USP48 domain was involved in the interaction, we performed co-immunoprecipitation experiments with either ARL3 or UNC119a and several USP48 proteins carrying different domain deletions."

36293380

USP48 affects TP53

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USP48 ubiquitinates TP53. 3 / 3

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"While the co-expression of Mdm2 and USP48 strongly enhanced p53 ubiquitination ( xref ), USP48 was not capable of inducing p53 ubiquitination in the absence of Mdm2 ( xref ), suggesting that the observed increase in Mdm2 levels was largely responsible for the enhancement of p53 ubiquitination in the presence of USP48."

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"Importantly, p53 degradation assay showed that the USP48-induced increase in Mdm2-mediated p53 ubiquitination could also lead to more efficient p53 degradation ( xref )."

28233861

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"USP48 can enhance Mdm2-mediated p53 ubiquitination and degradation."

28233861

Modified USP48 leads to the ubiquitination of TP53. 1 / 1

| 1

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"While the co-expression of Mdm2 and USP48 strongly enhanced p53 ubiquitination (XREF_FIG), USP48 was not capable of inducing p53 ubiquitination in the absence of Mdm2 (XREF_FIG), suggesting that the observed increase in Mdm2 levels was largely responsible for the enhancement of p53 ubiquitination in the presence of USP48."

28233861

USP48 affects NPPA

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NPPA binds USP48. 4 / 4

| 4

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"The related substances of SIM were measured by HPLC according to USP31-NF26, and the chromatographic conditions were the same with content analysis."

20801201

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"The new criteria from USP 〈905〉 Uniformity of Dosages Units ( USP31-NF29, 2009 ) harmonized with European Pharmacopoeia 2.9.40."

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"According to USP31-NF26, drug solubility is categorized into two major types: water-soluble drugs (including very soluble, freely soluble and soluble) with the solubility ≥1/30 g/ml, and water-insolub[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The content of SIM was analyzed according to the US Pharmacopoeia (USP31-NF26) by HPLC."

20801201

USP48 affects GPS1

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GPS1 binds USP48. 2 / 4

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"While, in human cells, USP15 specifically binds to CSN7A [ xref ] and consequently to the CSN CSN7A-USP15 -CRL3 BTB complex [ xref ], USP48 is associated with CSN1 [ xref ] but interacts mostly with CSN CSN7B-USP48 -CRL4A/B [ xref ]."

40149914

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"We found that deubiquitinylase (DUB) ubiquitin specific protease 48 (USP48), which interacts with the COP9 signalosome (CSN) subunit CSN1, stabilises RelA by deubiquitinylation and thereby promotes the transcriptional activity of RelA to prolong de novo synthesis of DUB A20 in H. pylori infection."

35913642

USP48 affects E3_Ub_ligase

| 4

USP48 inhibits E3_Ub_ligase.

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USP48 inhibits E3_Ub_ligase. 3 / 3

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"In cells we reveal that USP48 antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48 results in positioning 53BP1 further from the break site and in extended resection lengths."

29335415

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"For instance, USP48 might bind UNC119a and block the recognition site of the E3 ligase, preventing UNC119a from being ubiquitinated and targeted for proteasomal degradation."

36293380

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"Further, USP48 promotes cell survival and antagonizes also other E3 ligase functions which are involved in genome stability and DNA repair."

30628021

USP48 activates E3_Ub_ligase.

| 1

USP48 activates E3_Ub_ligase. 1 / 1

| 1

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"We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function."

29335415

USP48 affects Caspase

| 4

USP48 inhibits Caspase.

| 2

USP48 inhibits Caspase. 2 / 2

| 2

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"USP48 controls A20 de novo synthesis and suppresses caspase cleavages."

35913642

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"Conversely, transient transfection of USP48 protein before H. pylori infection suppressed cleavage of caspases (Fig. 3d)."

35913642

USP48 activates Caspase.

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USP48 activates Caspase. 2 / 2

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"Furthermore, transfection of A20 protein in USP48-depleted cells before H. pylori infection suppressed caspase cleavage and apoptotic cell death (Fig. 4c), indicating that the protective effect on apoptotic cell death is dependent on the expression of A20."

35913642

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"To test this hypothesis, we transiently transfected recombinant USP48 protein into A20 knockdown cells and found that USP48 rescued H. pylori-induced caspase cleavages in parental cells but not in A20-depleted cells (Fig. 4a)."

35913642

USP48 affects Carcinogenesis

| 4

USP48 activates Carcinogenesis.

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USP48 activates Carcinogenesis. 3 / 3

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"Intriguingly, GLI1 is the downstream target of sonic hedgehog (SHH) signaling that is deregulated in corticotroph tumors [57] indicating that both USP8 and USP48 might trigger corticotroph tumorigenesis via the same pathway."

31845722

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"It is therefore of interest to show that somatic activating pathogenic variants in the USP48 gene may induce corticotroph tumorigenesis by enhancing corticotroph tumor response to hypothalamic CRH stimulation.Among the potential USP48 substrates, Gli1 is of particular interest for corticotroph pathophysiology."

31222332

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"Additionally, USP48 has been shown to promote tumorigenesis by stabilizing oncoproteins such as Gli1, TRAF2, and Mdm2."

39878157

USP48 inhibits Carcinogenesis.

| 1

USP48 inhibits Carcinogenesis. 1 / 1

| 1

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"Knockdown of USP48 leads to the inhibition of Gli1 target gene expression, thereby suppressing cell proliferation and tumorigenesis."

40034124

USP48 affects CRH

| 4

USP48 activates CRH. 4 / 4

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"USP48 pathogenic variants are relatively frequent in USP8 wild-type tumors and enhance CRH-induced hormone production in a manner coherent with sonic hedgehog activation."

31222332

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"The USP48 variant identified potentiated the stimulatory action of hypothalamic corticotropin-releasing hormone (CRH) on ACTH synthesis in a GLI1-dependent manner."

31845722

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"Overexpression of USP48 wt potentiated the stimulatory CRH action (173% ± 13% for ACTH secretion and 171% ± 15% for POMC promoter activity vs CRH treated mock transfected controls, P < 0.01; representative example in Fig. 3D and E)."

31222332

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"Based on initial evidence in the literature, USP48 and USP8 mutations in PitNETs are believed to enhance corticotropin releasing hormone (CRH)-induced production coherent with the Hh signaling pathway (Fig 3E)."

36640905

USP48 affects AR/ARv7

| 4

AR/ARv7 binds USP48. 4 / 4

| 4

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"To further investigate how VAV2 regulates AR/ARv7 stabilization, the interaction between AR/ARv7 and USP48 was assessed following VAV2 depletion."

40303312

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reach

"Co-IP results demonstrated that VAV2 knockdown weakened the interaction between USP48 and AR/ARv7 (Fig. 8F)."

40303312

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reach

"These results collectively demonstrate that VAV2 stabilizes AR/ARv7 by enhancing the association between USP48 and AR/ARv7, thereby promoting Enzalutamide resistance."

40303312

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reach

"USP48 emerged as the only candidate common to both analyses, and co-IP assays confirmed interactions between USP48, VAV2, and AR/ARv7."

40303312

UNC119a affects USP48

| 4

USP48 binds UNC119a. 4 / 4

| 4

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"This result suggested that the CK2 domain, and to a minor extent the UBL domain, were crucial for the interaction between UNC119a and USP48.In summary, all our data support that USP48 can interact with and stabilise ARL3 and UNC119a using different mechanisms and distinct protein domains."

36293380

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"Alternatively, the DUB-independent regulation of UNC119a levels by USP48 could be hinting at an indirect interaction between UNC119a and USP48, through a third partner or via the formation of a stabilising complex with USP48, resulting in the stabilisation of UNC119a."

36293380

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"To study whether the interaction between USP48 and ARL3 and UNC119a was dependent on the USP48 DUB activity, the protein stability of these interactors was assayed in different conditions, and several USP48-derived constructs (USP48 , catalytically inactive USP48 or hyperactive USP48 )."

36293380

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"These results were consistent and independent of the epitope tag used (Figure S4), overall suggesting that the USP48 interaction and stabilisation of ARL3 and UNC119a occur by different mechanisms.In order to dissect which USP48 domain was involved in the interaction, we performed co-immunoprecipitation experiments with either ARL3 or UNC119a and several USP48 proteins carrying different domain deletions."

36293380

PR-619 affects USP48

| 4

PR-619 decreases the amount of USP48.

| 2

PR-619 decreases the amount of USP48. 2 / 2

| 2

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"However, little is known about effects and mechanism of PR-619 in AML.In this study, we demonstrated that PR-619 reduces USP48 protein levels by promoting its cleavage in various leukemia cells."

39878157

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"Western blot analysis revealed that PR-619 reduced USP48 protein levels and promoted PARP cleavage (Figure 1c)."

39878157

PR-619 activates USP48.

| 2

PR-619 activates USP48. 2 / 2

| 2

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"Additionally, USP48 cleavage was observed in AML cells treated with chemotherapy drugs HHT (Figure 1f) and Ara-C (Figure 1g), and during ATRA-induced differentiation in NB4 cells (Figure 1h), indicating that both PR-619 and chemotherapy drugs induce USP48 cleavage in AML."

39878157

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"We hypothesized that PR-619 and chemotherapy drugs induce USP48 cleavage through activated caspase-3."

39878157

POMC affects USP48

| 2 2

POMC increases the amount of USP48.

| 2

POMC increases the amount of USP48. 2 / 2

| 2

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"We next searched for the molecular mechanisms underlying USP48 mutation-mediated POMC transcription."

30093687

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"Collectively, these results demonstrate that the molecular mechanisms underlying USP48 mutation-mediated POMC transcription do not involve Erk1/2 or its downstream signaling cascade."

30093687

POMC activates USP48.

| 2

POMC activates USP48. 1 / 1

| 1

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"They also observed increased rodent Pomc promoter activity and Pomc mRNA expression in the mutated USP48 overexpressed-AtT-20 cells."

36672445

POMC activates mutated USP48. 1 / 1

| 1

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"We provide evidence that Gli1 is at least in part responsible for the increased ACTH synthesis in USP48 mutant corticotroph cells, while we suspect that USP48-induced H2A deubiquitination dissociates it from DNA damage repair proteins and deregulates DNA repair."

31222332

NPPA affects USP48

| 4

NPPA binds USP48. 4 / 4

| 4

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"The related substances of SIM were measured by HPLC according to USP31-NF26, and the chromatographic conditions were the same with content analysis."

20801201

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"The new criteria from USP 〈905〉 Uniformity of Dosages Units ( USP31-NF29, 2009 ) harmonized with European Pharmacopoeia 2.9.40."

19747967

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"According to USP31-NF26, drug solubility is categorized into two major types: water-soluble drugs (including very soluble, freely soluble and soluble) with the solubility ≥1/30 g/ml, and water-insolub[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

20933074

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"The content of SIM was analyzed according to the US Pharmacopoeia (USP31-NF26) by HPLC."

20801201

Hedgehog affects USP48

| 4

Hedgehog increases the amount of USP48. 4 / 4

| 4

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"Additionally, active HH signaling induces USP48 expression via a positive feedback loop by GLI1 binding to the USP48 promoter (203)."

37476499

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"In addition, we find that the Sonic Hedgehog (SHH) pathway induces USP48 expression through Gli1 mediated transcriptional activation, which forms thus a positive feedback loop to regulate Hh signaling."

28623188

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reach

"USP48 provides a positive feedback loop in Hh signaling as USP48 expression is induced by Hh activation."

30754706

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reach

"In addition, to a certain extent, GLI1 determines the effect of USP48 on cell proliferation and tumorigenesis and the HH pathway also induces USP48 expression via GLI1 trans-activation, thus forming a mutual feedback loop (73)."

35949611

GSK3B affects USP48

| 2 2

GSK3B phosphorylates USP48. 3 / 3

| 1 2

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"In response to TNF-α, serine phosphorylation of USP48 by GSK3β increases USP48 activity."

33466790

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"We have shown that GSK3β phosphorylates USP48, ultimately resulting increases in deubiquitinase activity ( xref )."

33400290

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"Exposure to TNFalpha caused GSK3beta mediated phosphorylation of USP48, leading to deubiquitination of TRAF2 in beas2B cells, increasing JNK signaling upon TNF-alpha-induction [XREF_BIBR]."

31208841

GSK3B phosphorylates USP48 on serine. 1 / 1

| 1

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"In response to TNF-alpha, serine phosphorylation of USP48 by GSK3beta increases USP48 activity."

33466790

GPS1 affects USP48

2 | 2

GPS1 binds USP48. 2 / 4

2 | 2

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"While, in human cells, USP15 specifically binds to CSN7A [ xref ] and consequently to the CSN CSN7A-USP15 -CRL3 BTB complex [ xref ], USP48 is associated with CSN1 [ xref ] but interacts mostly with CSN CSN7B-USP48 -CRL4A/B [ xref ]."

40149914

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➶

sparser

"We found that deubiquitinylase (DUB) ubiquitin specific protease 48 (USP48), which interacts with the COP9 signalosome (CSN) subunit CSN1, stabilises RelA by deubiquitinylation and thereby promotes the transcriptional activity of RelA to prolong de novo synthesis of DUB A20 in H. pylori infection."

35913642

AR/ARv7 affects USP48

| 4

AR/ARv7 binds USP48. 4 / 4

| 4

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"To further investigate how VAV2 regulates AR/ARv7 stabilization, the interaction between AR/ARv7 and USP48 was assessed following VAV2 depletion."

40303312

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reach

"Co-IP results demonstrated that VAV2 knockdown weakened the interaction between USP48 and AR/ARv7 (Fig. 8F)."

40303312

---

➶

reach

"These results collectively demonstrate that VAV2 stabilizes AR/ARv7 by enhancing the association between USP48 and AR/ARv7, thereby promoting Enzalutamide resistance."

40303312

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➶

reach

"USP48 emerged as the only candidate common to both analyses, and co-IP assays confirmed interactions between USP48, VAV2, and AR/ARv7."

40303312

VAV2 affects USP48

| 1 2

USP48 binds VAV2. 3 / 3

| 1 2

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"USP48 emerged as the only candidate common to both analyses, and co-IP assays confirmed interactions between USP48, VAV2, and AR/ARv7."

40303312

---

➶

sparser

"USP48 emerged as the only candidate common to both analyses, and co-IP assays confirmed interactions between USP48, VAV2, and AR/ARv7."

40303312

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sparser

"Co-IP assays confirmed direct interactions between USP48 and both VAV2 and AR/ARv7 (Fig. xref B-C)."

40303312

Ubiquitin affects USP48

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Ubiquitin activates USP48. 3 / 3

| 3

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"An auxiliary ubiquitin on the nucleosome promotes USP48 activity."

29335415

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"On both substrates the addition of free ubiquitin did activate USP48."

29335415

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"Detailed biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin that itself does not get cleaved, modulates USP48 activity, which has possible implications for its regulation in vivo."

29335415

USP48 affects cell differentiation

| 3

USP48 activates cell differentiation. 3 / 3

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"Deubiquitinase USP48 promotes ATRA induced granulocytic differentiation of acute promyelocytic leukemia cells."

29901102

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"In conclusion, the present study highlights the function of USP48 in the ATRA induced granulocytic differentiation of APL cells and provides a theoretical basis for identifying novel targets for differentiation therapy of APL."

29901102

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"In a study by LI et al., it was shown that the protein USP48 promotes granulocytic differentiation that ATRA induces, while miR-301a-3p inhibits this process by binding to and reducing USP48 translation [27]."

39048945

USP48 affects VAV2

| 1 2

USP48 binds VAV2. 3 / 3

| 1 2

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"USP48 emerged as the only candidate common to both analyses, and co-IP assays confirmed interactions between USP48, VAV2, and AR/ARv7."

40303312

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➶

sparser

"USP48 emerged as the only candidate common to both analyses, and co-IP assays confirmed interactions between USP48, VAV2, and AR/ARv7."

40303312

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sparser

"Co-IP assays confirmed direct interactions between USP48 and both VAV2 and AR/ARv7 (Fig. xref B-C)."

40303312

USP48 affects SLC9A3

| 3

USP48 activates SLC9A3.

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USP48 activates SLC9A3. 2 / 2

| 2

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"That is, the dopamine D3 receptor inhibits USP48 expression, which promotes NHE3 degradation."

26807585

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"USP48 silencing decreased NHE3 's half-life (USP48 siRNA t1/2 = 6.1 h vs. vehicle t1/2 = 12.9 h), whereas overexpression of USP48 increased NHE3 half-life (t1/2 = 21.8 h), indicating that USP48 protects NHE3 from degradation via deubiquitinylation."

24308971

USP48 inhibits SLC9A3.

| 1

USP48 inhibits SLC9A3. 1 / 1

| 1

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"That is, the dopamine D3 receptor inhibits USP48 expression, which promotes NHE3 degradation."

26807585

USP48 affects PKD1L3

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PKD1L3 binds USP48. 3 / 3

| 3

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"Therefore, we hypothesized that Hsp90 would be involved in CSFV-IRES and FMDV-IRES activities in association with eIF3c, and that both these proteins would interact with common host factors PKD1L3 and USP31."

40188851

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"We first fixed anti-PKD1L3 or USP31 antibodies ( xref A) and anti-Myc or anti-HA antibodies ( xref B) to Magnosphere™ gel to examine the interaction between PKD1L3 and USP31."

40188851

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"Immunoprecipitation assays revealed that PKD1L3 and USP31 can interact with each other."

40188851

USP48 affects Neoplasm Invasiveness

| 3

USP48 activates Neoplasm Invasiveness. 3 / 3

| 3

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"The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation."

32359336

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"Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis."

38572092

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"The results showed that USP48 overexpression significantly enhanced the migration and invasion abilities of CRC cells, while blocking HMGA2 expression reversed the phenotype caused by USP48 overexpression (Fig. 4H‒J and Fig. S4H‒J)."

38572092

USP48 affects MYC

| 3

USP48 binds MYC. 3 / 3

| 3

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"Myc-C98A and Myc-3S1T displayed similar nuclear localization as the full-length Myc-USP48."

37781625

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"Myc-USP48 truncation mutants (Δ1, Δ3, Δ4, Δ5, and Δ7) lacking indicated amino acid stretches ( xref ) retained their nuclear preference but mutants lacking amino acids 796–946 (Δ2 and Δ6) lost the nuclear localization capability and instead were enriched in the cytoplasm ( xref , xref )."

37781625

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"Similar results were observed when Myc-USP48 and mutants were expressed in HEK293T cells ( xref )."

37781625

USP48 affects ICL

| 3

USP48 inhibits ICL. 2 / 2

| 2

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"Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background."

29891926

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"Re-introduction of exogenous wild-type USP48, but not the catalytically inactive C98S USP48 mutant, partially reduced ICL resistance of DeltaUSP48DeltaFANCC cells, thus indicating that lack of USP48 catalytic activity is important for the increased survival of DeltaUSP48DeltaFANCC cells."

29891926

USP48-C98S inhibits ICL. 1 / 1

| 1

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"Re-introduction of exogenous wild-type USP48, but not the catalytically inactive C98S USP48 mutant, partially reduced ICL resistance of DeltaUSP48DeltaFANCC cells, thus indicating that lack of USP48 catalytic activity is important for the increased survival of DeltaUSP48DeltaFANCC cells."

29891926

USP48 affects Hedgehog

| 3

USP48 activates Hedgehog. 3 / 3

| 3

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"In addition to USP7 and OTUB2, the deubiquitinase USP48 was found to activate Hh signaling by stabilizing Gli1 protein in glioma cells [65]."

| PMC

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"However, the observation that USP8 and USP48 rather positively regulate HH signaling, whereas GNAS, MEN1, PRKAR1A, DICER1 and VHL rather negatively regulate this signaling pathway in PitNETs, does not allow a definitive conclusion, whether it is active or inactive HH signaling that is involved in formation of these tumors."

37476499

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"Conversely, the activation of HH signaling induced by the agonist purmorphamine results in an up-regulation of USP37 gene expression, subsequently leading to the stabilization of GLI1 and influencing EMT in breast CSCs.295 Furthermore, Zhou et al discovered that USP48, a deubiquitinase enzyme, activates the Hh signaling pathway by enhancing the stability of the Gli1 protein in glioma cells.296 Through its C-terminal DUSP structural domain, USP48 interacts with Gli1 and removes Ub molecules from it."

40034124

USP48 affects CDH1

| 3

USP48 increases the amount of CDH1.

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USP48 increases the amount of CDH1. 2 / 2

| 2

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"Further, down-regulation of USP48 increases E-cadherin expression and epithelial barrier integrity through reducing TRAF2 stability.-Li, S., Wang, D., Zhao, J., Weathington, N. M., Shang, D., Zhao, Y."

28874458

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"Inhibition of TRAF2 and JNK pathway increases E-cadherin expression and enhances epithelial barrier integrity, while knockdown of USP48 attenuates TNF-alpha and JNK pathway and increases E-cadherin expression and cell-cell junction in epithelial cells."

28874458

USP48 decreases the amount of CDH1.

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USP48 decreases the amount of CDH1. 1 / 1

| 1

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"In response to TNF-α, GSK3β-mediated serine phosphorylation can further enhance the deubiquitination activity of USP48, which in turn stabilizes the second messenger adaptor TRAF2 in the TNF-α pathway and ultimately suppresses E-cadherin expression [181]."

36998063

SIRT6 affects K48

| 3

USP48 binds SIRT6 and K48. 3 / 3

| 3

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"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis.Lipids include phospholipids, fatty acids, triglycerid[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

35798087

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"USP48 physically bound and stabilized SIRT6 by K48 linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

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➶

reach

"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

37127248

SHH affects USP48

| 1 2

SHH increases the amount of USP48. 3 / 3

| 1 2

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"To identify the signal mediating Shh-induced Usp31 overexpression, we first analyzed the promoter region of Usp31 ."

38342927

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reach

"In addition, we find that the Sonic Hedgehog (SHH) pathway induces USP48 expression through Gli1 mediated transcriptional activation, which forms thus a positive feedback loop to regulate Hh signaling."

28623188

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➶

sparser

"Interestingly, the knockdown of Gli1 did not affect Shh-induced Usp31 expression."

38342927

PKD1L3 affects USP48

| 3

PKD1L3 binds USP48. 3 / 3

| 3

---

➶

sparser

"Therefore, we hypothesized that Hsp90 would be involved in CSFV-IRES and FMDV-IRES activities in association with eIF3c, and that both these proteins would interact with common host factors PKD1L3 and USP31."

40188851

---

➶

sparser

"We first fixed anti-PKD1L3 or USP31 antibodies ( xref A) and anti-Myc or anti-HA antibodies ( xref B) to Magnosphere™ gel to examine the interaction between PKD1L3 and USP31."

40188851

---

➶

sparser

"Immunoprecipitation assays revealed that PKD1L3 and USP31 can interact with each other."

40188851

MYC affects USP48

| 3

USP48 binds MYC. 3 / 3

| 3

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➶

sparser

"Myc-C98A and Myc-3S1T displayed similar nuclear localization as the full-length Myc-USP48."

37781625

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➶

sparser

"Myc-USP48 truncation mutants (Δ1, Δ3, Δ4, Δ5, and Δ7) lacking indicated amino acid stretches ( xref ) retained their nuclear preference but mutants lacking amino acids 796–946 (Δ2 and Δ6) lost the nuclear localization capability and instead were enriched in the cytoplasm ( xref , xref )."

37781625

---

➶

sparser

"Similar results were observed when Myc-USP48 and mutants were expressed in HEK293T cells ( xref )."

37781625

K48 affects SIRT6, and USP48

| 3

USP48 binds SIRT6 and K48. 3 / 3

| 3

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➶

reach

"USP48 physically binds and stabilizes SIRT6 by K48-linked deubiquitination to impede glucose metabolic reprogramming and hamper HCC tumorigenesis.Lipids include phospholipids, fatty acids, triglycerid[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

35798087

---

➶

reach

"USP48 physically bound and stabilized SIRT6 by K48 linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis."

33903120

---

➶

reach

"Du et al. described that after being stabilized by methyltransferase-like 14 (Mettl14), USP48 binds and stabilizes SIRT6 by K48-linked deubiquitination of this SIRT (K33/K128)."

37127248

Cas9 affects USP48

| 1 1

Cas9 inhibits USP48. 2 / 2

| 1 1

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"Further confirming that the synthetic rescue was indeed dependent on USP48, when we subjected USP48 to short-hairpin RNA (shRNA) depletion (Supplementary Fig.  xref ) or carried out USP48 gene inactivation by CRISPR-Cas9 editing by using a different single guide (sg)RNA targeting a different exon (Supplementary Fig.  xref ) in Δ FANCC cells, we observed similar results."

29891926

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reach

"Construction of stable cell lines and CRISPR/Cas9-mediated USP48 knockout in stable cells and neurons.."

37781625

Bai affects USP48

| 1 1

Bai decreases the amount of USP48.

| 1

Bai decreases the amount of USP48. 1 / 1

| 1

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➶

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"These results show that BAI inhibited inflammation and oxidative stress by enhancing USP48 protein expression."

38245760

Bai binds USP48.

| 1

Bai binds USP48. 1 / 1

| 1

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➶

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"Second, it remains unclear whether BAI directly binds to USP48 or regulates USP48 through other pathways, necessitating further research to elucidate their regulatory mechanisms."

38245760

WNT5A affects USP48

| 1 1

USP48 binds WNT5A. 2 / 2

| 1 1

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➶

sparser

"Coimmunoprecipitation was used to examine the interaction between USP48 and Wnt5a."

38505871

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➶

reach

"Coimmunoprecipitation was used to examine the interaction between USP48 and Wnt5a."

38505871

USP48 affects signal transduction

| 2

USP48 activates signal transduction. 2 / 2

| 2

---

➶

reach

"Conversely, the activation of HH signaling induced by the agonist purmorphamine results in an up-regulation of USP37 gene expression, subsequently leading to the stabilization of GLI1 and influencing EMT in breast CSCs.295 Furthermore, Zhou et al discovered that USP48, a deubiquitinase enzyme, activates the Hh signaling pathway by enhancing the stability of the Gli1 protein in glioma cells.296 Through its C-terminal DUSP structural domain, USP48 interacts with Gli1 and removes Ub molecules from it."

40034124

---

➶

reach

"The signaling pathway mediated by the USP48–HMGA2 axis plays a critical role in promoting invasion and metastasis of CRC cells."

38572092

USP48 affects cell migration

| 2

USP48 activates cell migration. 2 / 2

| 2

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"Interestingly, we found that reconstitution of USP48 WT in endogenous USP48-deficient DLD1 cells significantly increased cell migration capacity as well as lung metastasis compared to the USP48 K258R mutant (Fig. 6L and M)."

38572092

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"The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation."

32359336

USP48 affects bai

| 1 1

USP48 binds bai.

| 1

Bai binds USP48. 1 / 1

| 1

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sparser

"Second, it remains unclear whether BAI directly binds to USP48 or regulates USP48 through other pathways, necessitating further research to elucidate their regulatory mechanisms."

38245760

USP48 activates bai.

| 1

USP48 activates bai. 1 / 1

| 1

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"BAI treatment promoted USP48 protein expression, and USP48 knockdown abrogated the protective effects of BAI, indicating that USP48 is a downstream mediator of BAI."

38245760

USP48 affects all-trans-retinoic acid

| 2

USP48 activates all-trans-retinoic acid. 2 / 2

| 2

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reach

"Deubiquitinase USP48 promotes ATRA induced granulocytic differentiation of acute promyelocytic leukemia cells [XREF_BIBR]."

30898977

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reach

"Deubiquitinase USP48 promotes ATRA induced granulocytic differentiation of acute promyelocytic leukemia cells."

29901102

USP48 affects WNT5A

| 1 1

USP48 binds WNT5A. 2 / 2

| 1 1

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"Coimmunoprecipitation was used to examine the interaction between USP48 and Wnt5a."

38505871

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reach

"Coimmunoprecipitation was used to examine the interaction between USP48 and Wnt5a."

38505871

USP48 affects Ubiquitin

| 2

USP48 inhibits Ubiquitin.

| 1

USP48 inhibits Ubiquitin. 1 / 1

| 1

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"USP48 has been identified to reverse this modification by specifically removing Ub at this site [122] (Figure 2C)."

38572758

USP48 activates Ubiquitin.

| 1

USP48 activates Ubiquitin. 1 / 1

| 1

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reach

"USP48 antagonizes ubiquitin-mediated autophagic degradation of MrgC and alleviates bone cancer pain in a murine animal model."

36864656

USP48 affects SLC1A5

| 2

USP48 increases the amount of SLC1A5.

| 1

USP48 increases the amount of SLC1A5. 1 / 1

| 1

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"Moreover, USP48 knockdown decreased SLC1A5 expression."

38427128

USP48 deubiquitinates SLC1A5.

| 1

USP48 deubiquitinates SLC1A5. 1 / 1

| 1

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reach

"USP48 overexpression deubiquitinated SLC1A5 to elevate cell proliferation and suppress cell apoptosis, inflammation, ferroptosis and oxidative stress in HG-triggered ARPE-19 cells, thereby inhibiting the progression of diabetic retinopathy."

38427128

USP48 affects PARP1

| 2

USP48 inhibits PARP1.

| 1

USP48 inhibits PARP1. 1 / 1

| 1

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reach

"Western blot analysis revealed that PR-619 reduced USP48 protein levels and promoted PARP cleavage (Figure 1c)."

39878157

USP48 activates PARP1.

| 1

USP48 activates PARP1. 1 / 1

| 1

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"After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells."

32359336

USP48 affects Mrgprx1

| 2

USP48 binds Mrgprx1.

| 1

USP48 binds Mrgprx1. 1 / 1

| 1

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"USP48 and MrgC interactions were studied by immunoprecipitation."

36864656

USP48 activates Mrgprx1.

| 1

USP48 activates Mrgprx1. 1 / 1

| 1

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➶

reach

"USP48 antagonizes ubiquitin-mediated autophagic degradation of MrgC and alleviates bone cancer pain in a murine animal model."

36864656

USP48 affects MAP3K7

| 2

USP48 inhibits MAP3K7.

| 1

USP48 inhibits MAP3K7. 1 / 1

| 1

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reach

"USP48 inhibits colorectal cancer progression and promotes M1-like macrophage polarization by stabilizing TAK1."

39971179

USP48 binds MAP3K7.

| 1

USP48 binds MAP3K7. 1 / 1

| 1

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reach

"Through deubiquitination, USP48 interacts with and stabilizes TAK1, leading to the inhibition of TAK1-triggered NF-κB activation and effectively suppresses CRC tumorigenesis."

39971179

USP48 affects Infections

| 2

USP48 activates Infections. 2 / 2

| 2

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"USP48 and A20 synergistically promote cell survival in Helicobacter pylori infection."

35913642

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➶

reach

"USP48 is implicated in activation of NF-κB (Mirra et al. 2022; Schweitzer and Naumann 2015; Ghanem et al. 2019), induces pyroptosis by stabilization of Gasdermin E (Ren et al. 2023) and promotes cell survival in Helicobacter pylori infection (Jantaree et al. 2022)."

39985644

USP48 affects Genomic Instability

| 2

USP48 activates Genomic Instability. 2 / 2

| 2

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"Importantly, the results of the present study show that loss of USP48 improves DNA repair and prevents genomic instability of FA defective cells, thus highlighting the potential of developing USP48 inhibitory molecules as novel therapeutic approaches that could potentially alleviate the phenotypes of FA patients."

29891926

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reach

"We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function."

29335415

USP48 affects G1 phase

| 2

USP48 activates G1 phase. 2 / 2

| 2

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reach

"Furthermore, inhibition of USP48 expression through shRNA knockdown in AML cell lines significantly reduced cell proliferation, promoted apoptosis, and induced G1 phase arrest."

39878157

---

➶

reach

"All the data indicated that inhibition of USP48 expression could decrease growth of AML cells by inducing apoptosis and G1 phase arrest."

39878157

USP48 affects FANCD2

| 2

USP48 ubiquitinates FANCD2.

| 1

USP48 leads to the ubiquitination of FANCD2. 1 / 1

| 1

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reach

"Since monoubiquitylation of components of the FANCI and FANCD2 complex is an important step of ICL repair XREF_BIBR, XREF_BIBR and considering that USP48 is a DUB, we tested whether USP48 depletion could rescue the FANCI and FANCD2 monoubiquitylation defect of DeltaFANCC cells."

29891926

USP48 deubiquitinates FANCD2.

| 1

Modified USP48 leads to the deubiquitination of FANCD2. 1 / 1

| 1

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reach

"Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background."

29891926

USP48 affects COPS7B

1 | 1

USP48 binds COPS7B. 1 / 2

1 | 1

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sparser

"While, in human cells, USP15 specifically binds to CSN7A [ xref ] and consequently to the CSN CSN7A-USP15 -CRL3 BTB complex [ xref ], USP48 is associated with CSN1 [ xref ] but interacts mostly with CSN CSN7B-USP48 -CRL4A/B [ xref ]."

40149914

USP48 affects ACVRL1

| 2

USP48 inhibits ACVRL1. 2 / 2

| 2

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reach

"Flow cytometry analysis also showed that both HHT and USP48 shRNA induced apoptosis of AML cells, HHT combined with USP48 shRNA enhances cell apoptosis (Figure 6c,d)."

39878157

---

➶

reach

"MTT experiments showed that both HHT and USP48 shRNA could inhibit AML cell proliferation, and inhibiting USP48 could enhance the effect of HHT (Figure 6b)."

39878157

USP48 affects ACE2

| 2

USP48 ubiquitinates ACE2.

| 1

USP48 leads to the ubiquitination of ACE2. 1 / 1

| 1

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reach

"In male mouse kidneys, ACE2 was distributed at sodium-hydrogen-exchanger-3 positive proximal-convoluted-tubules; ACE2-ubiquitination was decreased by candesartan, accompanied with increased ubiquitin-specific-protease-48 (USP48)."

38498345

USP48 activates ACE2.

| 1

USP48 activates ACE2. 1 / 1

| 1

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reach

"The silence of USP48 by siRNA caused a reduction of ACE2 in the cells."

38498345

TNF affects USP48

| 2

TNF phosphorylates USP48.

| 1

TNF leads to the phosphorylation of USP48. 1 / 1

| 1

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reach

"USP48 phosphorylation at its C-terminal CK2 phosphorylation sites in response to TNF was confirmed after knockdown of endogenous USP48, followed by reexpression of either siRNA resistant USP48-FL WT o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

TNF activates USP48.

| 1

TNF activates USP48. 1 / 1

| 1

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reach

"TNF induced degradation and reaccumulation of IkappaBalpha were not affected in USP48 depleted cells, indicating unperturbed upstream signaling to NF-kappaB activation."

25486460

NFkappaB affects USP48

| 1 1

NFkappaB binds USP48.

| 1

USP48 binds NFkappaB. 1 / 1

| 1

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"USP48 interacts with the transcription factor NF-κB, deubiquitinates NF-κB subunit p65 and promotes its stability and activation, and up-regulates NF-κB target genes known to inhibit synaptogenesis."

37781625

NFkappaB activates USP48.

| 1

NFkappaB activates USP48. 1 / 1

| 1

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"Consistent with diminished TNF induced nuclear accumulation and accelerated degradation of RelA in USP48 depleted cells, induction of NF-kappaB target gene expression was decreased and/or delayed, whe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

25486460

LINC00467 affects USP48

| 2

LINC00467 increases the amount of USP48. 2 / 2

| 2

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"LINC00467 could upregulate USP48 expression via sponging miR-299-5p."

32159247

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➶

reach

"LINC00467 enhances HNSCC progression by serving as a sponge of miR-299-5p to increase USP48 expression."

32159247

K48 affects GSDME

| 2

USP48 binds GSDME and K48. 2 / 2

| 2

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189 to promote pyroptosis in cancer55."

38572092

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➶

reach

"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189."

36607699

HDAC7 affects USP48

| 1 1

HDAC7 leads to the sumoylation of USP48. 2 / 2

| 1 1

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"Our findings demonstrated that HDAC4 and HDAC7 promoted the SUMOylation of USP48, while SENP5 cleaved it."

38572092

---

➶

sparser

"Our findings demonstrated that HDAC4 and HDAC7 promoted the SUMOylation of USP48, while SENP5 cleaved it."

38572092

HDAC4 affects USP48

| 1 1

HDAC4 leads to the sumoylation of USP48. 2 / 2

| 1 1

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"Our findings demonstrated that HDAC4 and HDAC7 promoted the SUMOylation of USP48, while SENP5 cleaved it."

38572092

---

➶

sparser

"Our findings demonstrated that HDAC4 and HDAC7 promoted the SUMOylation of USP48, while SENP5 cleaved it."

38572092

GSDME affects K48, and USP48

| 2

USP48 binds GSDME and K48. 2 / 2

| 2

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"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189 to promote pyroptosis in cancer55."

38572092

---

➶

reach

"USP48 bound GSDME and removed K48-linked ubiquitination at positions K120 and K189."

36607699

EVC affects USP48

| 1 1

EVC ubiquitinates USP48. 2 / 2

| 1 1

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sparser

"Besides USP7, we also tested the effect on EVC ubiquitination of USP48, another deubiquitinating enzyme known to regulate Hh signaling ( xref ; xref )."

37576597

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➶

reach

"Altogether, these data indicate that EVC proteins undergo ubiquitination, which is unaffected by USP7 but strongly depends on whether EVC-EVC2 find each other to form their heterodimeric and mutually stabilizing complex.Besides USP7, we also tested the effect on EVC ubiquitination of USP48, another deubiquitinating enzyme known to regulate Hh signaling (Zhou et al., 2017; Sanchez-Bellver et al., 2022)."

37576597

CTNNB1 affects USP48

| 2

USP48 binds CTNNB1. 2 / 2

| 2

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sparser

"Afterwards, Co-IP assay was performed to detect the interaction between USP48 and β-catenin proteins."

35413838

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➶

sparser

"Afterwards, Co-IP, RNA pulldown, and luciferase reporter assays verified the interaction of USP48 with β-catenin."

35413838

COPS7B affects USP48

1 | 1

USP48 binds COPS7B. 1 / 2

1 | 1

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➶

sparser

"While, in human cells, USP15 specifically binds to CSN7A [ xref ] and consequently to the CSN CSN7A-USP15 -CRL3 BTB complex [ xref ], USP48 is associated with CSN1 [ xref ] but interacts mostly with CSN CSN7B-USP48 -CRL4A/B [ xref ]."

40149914

Μmol/L BAI affects USP48

| 1

Μmol/L BAI decreases the amount of USP48. 1 / 1

| 1

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➶

reach

"In summary, 20 µmol/L BAI treatment improved cell proliferation and reduced oxidative stress and inflammation by enhancing USP48 protein expression in 100 µmol/L H O -stimulated KGN cells."

38245760

ubiquitin-specific peptidase 48 affects USP48

| 1

Ubiquitin-specific peptidase 48 activates USP48. 1 / 1

| 1

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➶

reach

"In human renal proximal tubule cells and rat renal cortices, D R decreases NHE3 expression by increasing its degradation caused by the inhibition of the deubiquitinylating activity of ubiquitin-specific peptidase 48 (USP48) [86] (Figure 1)."

37009199

Transforming growth factor affects USP48

| 1

USP48 binds transforming growth factor. 1 / 1

| 1

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sparser

"The interaction between USP48 and Transforming growth factor-β activated kinase-1(TAK1) was confirmed using co-IP."

39971179

Short hairpin RNA affects USP48

| 1

Short hairpin RNA inhibits USP48. 1 / 1

| 1

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sparser

"We then demonstrate that inhibition of USP48 by shRNA or its newly discovered inhibitor DUB-IN-2 triggers HMGA2 degradation, thereby inhibiting CRC cell metastasis in vitro and in vivo ."

38572092

ProBDNF affects USP48

| 1

ProBDNF activates USP48. 1 / 1

| 1

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"Our observations that endogenous p65 level is required for normal synapse formation but USP48 overexpression strikingly inhibits synapse formation in a p65-dependent manner can be explained by USP48-dependent up-regulation of a subset of NF-κB target genes, including proBDNF and Caspase-3."

37781625

MiR-301a-3p affects USP48

| 1

MiR-301a-3p activates USP48. 1 / 1

| 1

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"In a study by LI et al., it was shown that the protein USP48 promotes granulocytic differentiation that ATRA induces, while miR-301a-3p inhibits this process by binding to and reducing USP48 translation [27]."

39048945

Dopamine affects USP48

| 1

Dopamine decreases the amount of USP48. 1 / 1

| 1

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➶

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"That is, the dopamine D3 receptor inhibits USP48 expression, which promotes NHE3 degradation."

26807585

Cell differentiation affects USP48

| 1

Cell differentiation activates USP48. 1 / 1

| 1

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reach

"Additionally, USP48 cleavage was observed in AML cells treated with chemotherapy drugs HHT (Figure 1f) and Ara-C (Figure 1g), and during ATRA-induced differentiation in NB4 cells (Figure 1h), indicating that both PR-619 and chemotherapy drugs induce USP48 cleavage in AML."

39878157

Caspase-3 inhibitor affects USP48

| 1

Caspase-3 inhibitor activates USP48. 1 / 1

| 1

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reach

"Western blot analysis confirmed that the caspase-3 inhibitor reduced PARP and USP48 cleavage after PR-619 treatment (Figure 2b)."

39878157

Casein-kinase 2 affects USP48

| 1

Casein-kinase 2 phosphorylates USP48. 1 / 1

| 1

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➶

reach

"The activity of UPS48 on NF-kappaB is enhanced by casein-kinase 2 mediated phosphorylation of USP48 which occurs following TNFalpha stimulation."

27187478

Casein affects USP48

| 1

Casein phosphorylates USP48. 1 / 1

| 1

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➶

sparser

"The activity of UPS48 on NF-κB is enhanced by casein-kinase 2 mediated phosphorylation of USP48 which occurs following TNFα stimulation."

27187478

AraC affects USP48

| 1

AraC activates USP48. 1 / 1

| 1

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➶

reach

"These effects were also observed with the use of chemotherapy drugs such as HHT, Ara-C, and ATRA, which induced the cleavage of USP48, thereby enhancing drug-induced apoptosis."

39878157

All-trans-retinoic acid affects USP48

| 1

All-trans-retinoic acid activates USP48. 1 / 1

| 1

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➶

reach

"These effects were also observed with the use of chemotherapy drugs such as HHT, Ara-C, and ATRA, which induced the cleavage of USP48, thereby enhancing drug-induced apoptosis."

39878157

USP7 affects USP48

| 1

USP7 binds USP25 and USP48. 1 / 1

| 1

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➶

sparser

"Among them, USP7, USP21, and USP48 have been associated with HR xref – xref ."

30874560

USP48

| 1

USP48 translocates to the nucleus. 1 / 1

| 1

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➶

sparser

"Furthermore, the expression of USP48 was increased in the nucleus upon ATRA exposure for ≤24 h, suggesting that USP48 was translocated into the nucleus."

29901102

USP48 affects vivo.3

| 1

USP48 activates vivo.3. 1 / 1

| 1

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➶

reach

"Collectively, these findings suggest that USP48 enhances tumor metastasis largely by regulating HMGA2 in vitro and in vivo.3."

38572092

USP48 affects ubiquitination

| 1

USP48 inhibits ubiquitination. 1 / 1

| 1

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➶

sparser

"Collectively, these data indicated that USP48 inhibits TNF-induced RelA ubiquitination through its DUB activity."

25486460

USP48 affects transforming growth factor

| 1

USP48 binds transforming growth factor. 1 / 1

| 1

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➶

sparser

"The interaction between USP48 and Transforming growth factor-β activated kinase-1(TAK1) was confirmed using co-IP."

39971179

USP48 affects transcription encoding proopiomelanocortin

| 1

USP48 activates transcription encoding proopiomelanocortin. 1 / 1

| 1

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➶

eidos

"Similar to USP8 mutants , both USP48 and BRAF mutants enhance the promoter activity and transcription of the gene encoding proopiomelanocortin ( POMC ) , which is the precursor of ACTH ."

30093687

USP48 affects transcription encoding proopiomelanocortin POMC is precursor ACTH potential mechanism ACTH overproduction

| 1

USP48 activates transcription encoding proopiomelanocortin POMC is precursor ACTH potential mechanism ACTH overproduction. 1 / 1

| 1

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➶

eidos

"Similar to USP8 mutants , both USP48 and BRAF mutants enhance the promoter activity and transcription of the gene encoding proopiomelanocortin ( POMC ) , which is the precursor of ACTH , providing a potential mechanism for ACTH overproduction in corticotroph adenomas ."

30093687

USP48 affects sodium atom

| 1

USP48 activates sodium atom. 1 / 1

| 1

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➶

reach

"We now offer and describe a novel mechanism by which D3R decreases sodium transport in the long term by inhibiting the deubiquitinylating activity of ubiquitin specific peptidase 48 (USP48), thereby promoting Na (+)-H (+) exchanger (NHE) -3 degradation."

24308971

USP48 affects sirtuins 6

| 1

USP48 leads to the deubiquitination of sirtuins 6. 1 / 1

| 1

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➶

reach

"The elevated USP48 further repress the ubiquitination of sirtuins 6 (SIRT6), therefore mitigating aerobic glycolysis and hindering tumor metastasis in HCC [89]."

38293446

USP48 affects runx1

| 1

USP48 activates runx1. 1 / 1

| 1

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➶

reach

"USP48 cleavage in drug induced apoptosis of AML."

39878157

USP48 affects responsiveness

| 1

USP48 inhibits responsiveness. 1 / 1

| 1

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➶

eidos

"The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP , and alleviates the metastasis in vivo ."

32359336

USP48 affects pathogenesis

| 1

Mutated USP48 activates pathogenesis. 1 / 1

| 1

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➶

reach

"The discovery of recurrent USP8 and USP48 mutations [4,5,6] allowed researchers to get some insight in the pathogenesis of corticotroph PitNETs [7]."

36428684

USP48 affects inflammatory response

| 1

USP48 inhibits inflammatory response. 1 / 1

| 1

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➶

reach

"USP48 knockdown promoted inflammation, oxidative stress, and apoptosis in BAI-treated H O -stimulated KGN cells, indicating that USP48 knockdown abrogated the protective effects of BAI."

38245760

USP48 affects homeostatic process

| 1

USP48 activates homeostatic process. 1 / 1

| 1

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➶

reach

"USP48 then stabilized sirtuin 6 proteins to prevent metabolic reprogramming from mitochondrial respiration toward aerobic glycolysis, then enhanced glycolytic homeostasis and inhibited tumor growth (84)."

37539726

USP48 affects gene expression

| 1

USP48 activates gene expression. 1 / 1

| 1

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➶

reach

"It will be interesting to investigate whether USP48-dependent deubiquitination contributes to constitutive NF-κB activity in neurons and fine-tunes NF-κB dependent gene expression during early neuronal and synaptic development.Our study reveals a DUB-mediated nuclear mechanism that bidirectionally drives synapse remodeling: increasing the full-length USP48 expression reduces spine density, inhibits spine maturation, and markedly decreases functional synapse numbers and weakens synaptic efficacy in vivo, whereas decreasing USP48 expression has largely opposite effects."

37781625

USP48 affects exogenous USP48-flag protein

| 1

USP48 activates exogenous USP48-flag protein. 1 / 1

| 1

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➶

reach

"Overexpression of flag-tagged USP48 in NB4 cells also showed that PR-619 induced cleavage of exogenous USP48-flag protein (Figure 1e)."

39878157

USP48 affects cortisol

| 1

Mutated USP48 activates cortisol. 1 / 1

| 1

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➶

reach

"BRAF and USP48 mutations increase in vitro POMC transcription and potentiate the stimulation effect of upstream cortisol-releasing hormone (CRH) [50,51]."

36612109

USP48 affects corticotropin secretion

| 1

USP48 activates corticotropin secretion. 1 / 1

| 1

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➶

reach

"In this respect, further studies investigating the roles of USPs in UPS are required.Hyperactive mutations of Usp8 and Usp48 cause excessive ACTH secretion from corticotroph adenomas, implying that USP8 and 48 have the potential to modulate the hypothalamus-pituitary-adrenal axis under physiological conditions."

36834633

USP48 affects chromatin remodeling

| 1

USP48 inhibits chromatin remodeling. 1 / 1

| 1

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➶

reach

"Notably, the authors in this study showed the activity of USP48 counteracts BRCA1 mediated ubquitylation of H2A K127/129 and thereby preventing chromatin remodeling and resection during double-strand break repair after IR and camptothecin treatment 35."

29891926

USP48 affects cell survival Helicobacter pylori infection

| 1

USP48 activates cell survival Helicobacter pylori infection. 1 / 1

| 1

---

➶

eidos

"USP48 and A20 synergistically promote cell survival in Helicobacter pylori infection ."

35913642

USP48 affects activation

| 1

USP48 inhibits activation. 1 / 1

| 1

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➶

sparser

"USP31 also inhibited NF-κB activation mediated by two TRAF proteins (TRAF2 and TRAF6), as well as by the IKKβ kinase ()."

16214042

USP48 affects abundance lysine K48 linked ubiquitination K63-linked ubiquitination TRAF2 stability

| 1

USP48 activates abundance lysine K48 linked ubiquitination K63-linked ubiquitination TRAF2 stability. 1 / 1

| 1

---

➶

eidos

"Surprisingly , USP48 knockdown increased the abundance of lysine 48 ( K48 ) - linked ubiquitination but not the K63-linked ubiquitination of TRAF2 , and subsequently reduced its stability ( Li et al ., 2018b ) ."

33224951

USP48 affects Wnt/β-catenin

| 1

USP48 activates Wnt/β-catenin. 1 / 1

| 1

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➶

reach

"This study revealed that miR-26b-5p regulates AML progression, possibly by targeting the USP48-mediated Wnt/β-catenin molecular axis to affect AML cell biological behavior."

38505871

USP48 affects USP7

| 1

USP7 binds USP25 and USP48. 1 / 1

| 1

---

➶

sparser

"Among them, USP7, USP21, and USP48 have been associated with HR xref – xref ."

30874560

USP48 affects USP

| 1

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

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➶

sparser

"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

USP48 affects TYRP1

| 1

USP48 binds TYRP1. 1 / 1

| 1

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➶

reach

"Here, we report that USP48 interacts with and stabilizes the Aurora B protein."

34445214

USP48 affects TP53BP1

| 1

USP48 inhibits TP53BP1. 1 / 1

| 1

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➶

reach

"USP48 loss increases resection and intriguingly, depletion of USP48 or 53BP1 or their co-depletion, all result in a similar increase in RAD51 foci, suggesting that loss of either protein has a similar impact and acts in the same pathway to restrict RAD51 accumulation."

29335415

USP48 affects TNF

| 1

USP48 activates TNF. 1 / 1

| 1

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➶

reach

"Previous reports have demonstrated that USP48 silencing downregulates TNFα –mediated NF-κB activation in vitro in non-retinal cells [17]."

36077078

USP48 affects Stomach Neoplasms

| 1

USP48 activates Stomach Neoplasms. 1 / 1

| 1

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➶

reach

"Together, USP48 and A20 promoted GC cell survival during H. pylori infection and suggested an oncogenic role for A20."

36497313

USP48 affects SMARCAD1

| 1

USP48 activates SMARCAD1. 1 / 1

| 1

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➶

reach

"Our data suggest a model in which USP48 mediated removal of the H2A BRCA1ub mark on chromatin restrains subsequent SMARCAD1 function, thereby halting the mobilization of 53BP1 and providing a boundary for resection."

29335415

USP48 affects SIM

| 1

USP48 binds SIM. 1 / 1

| 1

---

➶

sparser

"We hypothesize that the SUMOylation of USP48 may interact with a non-classically conserved SIM motif (V-V-Q-K) in the HMGA2 protein, or induce conformational changes in USP48 to better accommodate the HMGA2 protein xref ."

38572092

USP48 affects RPA

| 1

USP48 activates RPA. 1 / 1

| 1

---

➶

reach

"Irradiated S-phase cells depleted of USP48 had more RPA foci compared with controls and complementation with either siRNA resistant USP48 Iso1 -WT or USP48 Iso2 -WT, but not USP48 Iso2 -C98S, restored RPA foci numbers to control levels."

29335415

USP48 affects RO60

| 1

USP48 inhibits RO60. 1 / 1

| 1

---

➶

reach

"Moreover, we provide evidence that USP48 acts to prevent extensive resection and restrict the use of SSA."

29335415

USP48 affects REL

| 1

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

---

➶

sparser

"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

USP48 affects RAD51

| 1

USP48 inhibits RAD51. 1 / 1

| 1

---

➶

reach

"USP48 loss enhances BRCA1 and RAD51 localization in FA cells."

29891926

USP48 affects ProBDNF

| 1

USP48 increases the amount of ProBDNF. 1 / 1

| 1

---

➶

reach

"In contrast, USP48 knockdown significantly reduced Caspase 3 and ProBDNF expression, without altering other genes (Figure 7I, J)."

37781625

USP48 affects Pituitary ACTH Hypersecretion

| 1

USP48 activates Pituitary ACTH Hypersecretion. 1 / 1

| 1

---

➶

eidos

"In this study the authors report USP48 and BRAF are frequently mutated in USP8 wild-type corticotroph adenomas , and cause Cushing 's disease mainly through promoting the promoter activity of POMC ."

30093687

USP48 affects Pathway

| 1

USP48 activates Pathway. 1 / 1

| 1

---

➶

sparser

"USP31 Activates the Wnt/β-catenin Signaling Pathway and Promotes Gastric Cancer Cell Proliferation, Invasion and Migration."

38715330

USP48 affects POMC promoter

| 1

USP48 activates POMC promoter. 1 / 1

| 1

---

➶

reach

"A luciferase report assay showed that USP48 M415I/V promoted the POMC promoter activity."

30093687

USP48 affects POMC gene

| 1

USP48 increases the amount of POMC gene. 1 / 1

| 1

---

➶

reach

"Accordingly, USP48-mediated inhibition of NF-κB activity could promote the transcription of POMC gene."

30093687

USP48 affects PD-1 inhibitors

| 1

USP48 inhibits PD-1 inhibitors. 1 / 1

| 1

---

➶

reach

"Finally, overexpression of USP48 enhanced the therapeutic efficacy of PD-1 inhibitors in tumors in mouse models."

36607699

USP48 affects PCNA

| 1

USP48 increases the amount of PCNA. 1 / 1

| 1

---

➶

reach

"We performed western blot analysis on cellular extracts obtained from both siUSP48-transfected cells and control cells, stimulated with TNFα at different time points, and found that USP48 downregulation slightly increased PCNA expression (indicative of an NF-κB positive regulation), and reduced the expression of Cyclin E (indicative of an NF-κB negative regulation), in no TNFα-treated cells."

36077078

USP48 affects Mdm2 stability

| 1

USP48 activates Mdm2 stability. 1 / 1

| 1

---

➶

eidos

"In addition to USP2 , USP48 has also been shown recently to contribute to Mdm2 stability to enhance Mdm2-mediated degradation of p53119 ."

32201366

USP48 affects MDC1

| 1

USP48 binds MDC1. 1 / 1

| 1

---

➶

sparser

"On the other hand, the five most frequently selected pairs by the agnostic k-TSPs were MDC1-DECR1 (n = 75), MDC1-USP31 (n = 50), CPSF4-RPP40 (n = 43), CHSY1-NIF3L1 (n = 41), and SAC3D1-RPP40 (n = 37) ( xref B)."

36852282

USP48 affects JNK

| 1

USP48 inhibits JNK. 1 / 1

| 1

---

➶

reach

"However, in this study the authors showed that USP48 inhibits only JNK signaling upon TNFR1 stimulation in epithelial cells but does not affect NF-κB, MAPK and cell death signaling [54] indicating mutually nonexclusive cell type- and DUB-specific functions of USP48 and OTUD7b with respect to the regulation of TRAF2.The formation of the apoptosis-inducing complex-IIa (RIPK1-independent) and complex-IIb (RIPK1-dependent) is induced by insufficient pro-survival signals from complex-I [55]."

37516734

USP48 affects IKBKB

| 1

USP48 inhibits IKBKB. 1 / 1

| 1

---

➶

reach

"Initial studies found that overexpression of USP48 inhibits NF-kappaB activity downstream of IKKbeta and that USP48 also interacts with p65."

27187478

USP48 affects Glioma

| 1

USP48 activates Glioma. 1 / 1

| 1

---

➶

reach

"Conversely, the activation of HH signaling induced by the agonist purmorphamine results in an up-regulation of USP37 gene expression, subsequently leading to the stabilization of GLI1 and influencing EMT in breast CSCs.295 Furthermore, Zhou et al discovered that USP48, a deubiquitinase enzyme, activates the Hh signaling pathway by enhancing the stability of the Gli1 protein in glioma cells.296 Through its C-terminal DUSP structural domain, USP48 interacts with Gli1 and removes Ub molecules from it."

40034124

USP48 affects GRIA2

| 1

USP48 decreases the amount of GRIA2. 1 / 1

| 1

---

➶

reach

"Biotinlyation experiments further showed that surface levels of GluA1 and GluA2 were also increased by USP48 knockdown (Figure S5A, B)."

37781625

USP48 affects GRIA1

| 1

USP48 decreases the amount of GRIA1. 1 / 1

| 1

---

➶

reach

"Biotinlyation experiments further showed that surface levels of GluA1 and GluA2 were also increased by USP48 knockdown (Figure S5A, B)."

37781625

USP48 affects GPX4

| 1

GPX4 binds USP48. 1 / 1

| 1

---

➶

sparser

"Furthermore, GPX4 protein specifically binds the deubiquitinase USP31, but not other deubiquitinases such as CYLD, USP1, USP14, USP20, USP30, USP38, UCHL1, UCHL3, and UCHL5."

37011699

USP48 affects GC

| 1

USP48 inhibits GC. 1 / 1

| 1

---

➶

reach

"Thus, high levels or activity of USP48 would be expected to decrease resection lengths and thus reduce GC, and phenocopy aspects of BRCA1 loss."

29335415

USP48 affects FSCN1

| 1

USP48 inhibits FSCN1. 1 / 1

| 1

---

➶

reach

"Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background."

29891926

USP48 affects FASLG

| 1

USP48 activates FASLG. 1 / 1

| 1

---

➶

reach

"In conclusion, the present study highlights the function of USP48 in the ATRA induced granulocytic differentiation of APL cells and provides a theoretical basis for identifying novel targets for differentiation therapy of APL."

29901102

USP48 affects FANCI

| 1

Modified USP48 leads to the deubiquitination of FANCI. 1 / 1

| 1

---

➶

reach

"Our data demonstrate that loss of USP48 does not restore FANCI and FANCD2 monoubiquitylation or FANCD2 recruitment at ICLs, but if USP48 targets one or more sites on H2A that can be recognized by these nucleases, then loss of USP48 might bypass the requirement of the FA proteins and allow the recruitment of FAN1 or SLX4 and subsequent unhooking of the ICL in an FA deficient background."

29891926

USP48 affects F3

| 1

USP48 binds F3. 1 / 1

| 1

---

➶

sparser

"USP31 could serve as a potential biomarker for predicting both prognosis and immune responses, revealing its potential mechanisms of TF-USP31 mRNA networks in ccRCC."

37699648

USP48 affects ESS2

| 1

USP48 activates ESS2. 1 / 1

| 1

---

➶

reach

"The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation."

32359336

USP48 affects EIF3C

| 1

USP48 binds EIF3C. 1 / 1

| 1

---

➶

sparser

"PKD1L3 and more pronouncedly USP31 can interact with eIF3c."

40188851

USP48 affects EGFR

| 1

USP48 increases the amount of EGFR. 1 / 1

| 1

---

➶

reach

"Moreover, EGFR overexpression, caused by the USP48 and BRAF genes, could subsequently enhance cell proliferation and tumor growth in PAs [110]."

35454025

USP48 affects Diabetic Retinopathy

| 1

USP48 activates Diabetic Retinopathy. 1 / 1

| 1

---

➶

reach

"USP48 overexpression deubiquitinated SLC1A5 to elevate cell proliferation and suppress cell apoptosis, inflammation, ferroptosis and oxidative stress in HG-triggered ARPE-19 cells, thereby inhibiting the progression of diabetic retinopathy."

38427128

USP48 affects Deubiquitinase

| 1

Sumoylated USP48 activates Deubiquitinase. 1 / 1

| 1

---

➶

reach

"Although we failed to identify a conserved SIM motif in HMGA2, our findings demonstrated that the SUMOylated USP48 could still strongly interact with HMGA2, thereby enhancing the affinity of USP48 for ubiquitin chains and augmenting its DUB activity."

38572092

USP48 affects DUSP3

| 1

DUSP3 binds USP48. 1 / 1

| 1

---

➶

sparser

"DNA sequences encoding the following residues from each USP were cloned into a pET-21b vector using Gibson Assembly 45 : USP4-DUSP, 8–129; USP15-DUSP, 1–125; USP11-DUSP, 71–191; USP20-DUSP1, 687–780; [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

34666042

USP48 affects DUSP1

| 1

DUSP1 binds USP48. 1 / 1

| 1

---

➶

sparser

"DNA sequences encoding the following residues from each USP were cloned into a pET-21b vector using Gibson Assembly 45 : USP4-DUSP, 8–129; USP15-DUSP, 1–125; USP11-DUSP, 71–191; USP20-DUSP1, 687–780; [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

34666042

USP48 affects DUSP

| 1

USP48 activates DUSP. 1 / 1

| 1

---

➶

reach

"Conversely, the activation of HH signaling induced by the agonist purmorphamine results in an up-regulation of USP37 gene expression, subsequently leading to the stabilization of GLI1 and influencing EMT in breast CSCs.295 Furthermore, Zhou et al discovered that USP48, a deubiquitinase enzyme, activates the Hh signaling pathway by enhancing the stability of the Gli1 protein in glioma cells.296 Through its C-terminal DUSP structural domain, USP48 interacts with Gli1 and removes Ub molecules from it."

40034124

USP48 affects DNA-templated transcription

| 1

Mutated USP48 activates DNA-templated transcription. 1 / 1

| 1

---

➶

reach

"We next searched for the molecular mechanisms underlying USP48 mutation-mediated POMC transcription."

30093687

USP48 affects DNA repair

| 1

USP48 inhibits DNA repair. 1 / 1

| 1

---

➶

reach

"We next determined whether the effect of USP48 loss on survival of FA defective cells after treatment with DNA crosslinking agents correlated with less DNA damage induction and/or increased DNA repair."

29891926

USP48 affects DLG4

| 1

USP48 inhibits DLG4. 1 / 1

| 1

---

➶

reach

"USP48 downregulation of PSD-95 is somewhat surprising because NF-κB has been shown to turn on PSD-95 transcription (Boersma et al., 2011)."

37781625

USP48 affects Cell Plasticity

| 1

USP48 inhibits Cell Plasticity. 1 / 1

| 1

---

➶

eidos

"We identified a ubiquitin hydrolase , usp-48 , that restricts cellular plasticity with a notable cellular specificity ."

33877339

USP48 affects Carcinoma, Hepatocellular

| 1

USP48 activates Carcinoma, Hepatocellular. 1 / 1

| 1

---

➶

reach

"In hepatocellular carcinoma, the expression of USP48 is down-regulated, which is regulated by Mettl14-induced m6A modification and subsequently stabilizes SIRT6 to attenuate HCC glycolysis and malignancy39."

38572092

USP48 affects CSN1S1

| 1

USP48 binds CSN1S1. 1 / 1

| 1

---

➶

reach

"It was recently reported that the deubiquitinylase ubiquitin-specific protease 48 (USP48) interacts with constitutive photomorphogenesis 9 signalosome subunit 1 (CSN1) to stabilize RelA by deubiquitin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37230895

USP48 affects CREBBP

| 1

USP48 inhibits CREBBP. 1 / 1

| 1

---

➶

reach

"The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo."

32359336

USP48 affects COPS5

| 1

USP48 binds COPS5. 1 / 1

| 1

---

➶

sparser

"A recent study showed that USP48 associates with the COP9 signalosome complex and promotes the nuclear accumulation of NF-κB RelA through its DUB activity, trimming K48-linked ubiquitin chains xref ."

28233861

USP48 affects CASP8

| 1

USP48 activates CASP8. 1 / 1

| 1

---

➶

reach

"These data suggest that USP48 can promote deubiquitinylation of caspase-8 and impair caspase-8 activity."

35913642

USP48 affects BRCA1-H2Aub-SMARCAD1

| 1

USP48 inhibits BRCA1-H2Aub-SMARCAD1. 1 / 1

| 1

---

➶

reach

"USP48 antagonizes the BRCA1-H2Aub-SMARCAD1 resection pathway."

29335415

USP48 affects BRCA1-BARD1

| 1

USP48 inhibits BRCA1-BARD1. 1 / 1

| 1

---

➶

reach

"Consistent with a role for USP48 in antagonizing BRCA1-BARD1, USP48 depleted cells have higher numbers of RAD51 and RPA foci and these foci were more intense following IR."

32708614

USP48 affects BMAL1

| 1

USP48 binds BMAL1. 1 / 1

| 1

---

➶

sparser

"We then validated the binding of Bmal1 to the Usp31 promoter region."

38342927

USP48 affects BLNK

| 1

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

---

➶

sparser

"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

USP48 affects AR/ARv7 protein

| 1

USP48 increases the amount of AR/ARv7 protein. 1 / 1

| 1

---

➶

reach

"Furthermore, USP48 knockdown significantly reduced AR/ARv7 protein levels without affecting VAV2 expression (Fig. 8D-E)."

40303312

USP48 affects A20 apoptotic cell death cells infected H. pylori

| 1

USP48 inhibits A20 apoptotic cell death cells infected H. pylori. 1 / 1

| 1

---

➶

eidos

"USP48 thus enhances the activity of A20 to reduce apoptotic cell death in cells infected with H. pylori ."

35913642

USP48 affects )-H(+) exchanger

| 1

USP48 activates )-H(+) exchanger. 1 / 1

| 1

---

➶

reach

"We now offer and describe a novel mechanism by which D3R decreases sodium transport in the long term by inhibiting the deubiquitinylating activity of ubiquitin specific peptidase 48 (USP48), thereby promoting Na (+)-H (+) exchanger (NHE) -3 degradation."

24308971

USP25 affects USP7

| 1

USP7 binds USP25 and USP48. 1 / 1

| 1

---

➶

sparser

"Among them, USP7, USP21, and USP48 have been associated with HR xref – xref ."

30874560

USP affects USP48

| 1

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

---

➶

sparser

"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

TYRP1 affects USP48

| 1

USP48 binds TYRP1. 1 / 1

| 1

---

➶

reach

"Here, we report that USP48 interacts with and stabilizes the Aurora B protein."

34445214

SLC9A3 affects USP48

| 1

SLC9A3 inhibits USP48. 1 / 1

| 1

---

➶

reach

"We found that stimulation with the D3R specific agonist PD128907 (1 muM, 30 min) promoted the interaction and colocalization among D3R, NHE3, and USP48; inhibited USP48 activity (-35+/-6%, vs. vehicle), resulting in increased ubiquitinylated NHE3 (+140 +/-10%); and decreased NHE3 expression (-50+/-9%) in human renal proximal tubule cells (hRPTCs)."

24308971

SLC1A5 affects USP48

| 1

SLC1A5 inhibits USP48. 1 / 1

| 1

---

➶

reach

"SLC1A5 downregulation reversed the improvement effects of USP48 upregulation on cell damage in HG-treated ARPE-19 cells."

38427128

SIM affects USP48

| 1

USP48 binds SIM. 1 / 1

| 1

---

➶

sparser

"We hypothesize that the SUMOylation of USP48 may interact with a non-classically conserved SIM motif (V-V-Q-K) in the HMGA2 protein, or induce conformational changes in USP48 to better accommodate the HMGA2 protein xref ."

38572092

SENP5 affects USP48

| 1

SENP5 leads to the desumoylation of USP48. 1 / 1

| 1

---

➶

reach

"Co-expression of HDAC4 or HDAC7 facilitated the SUMOylation of USP48 protein (Fig. 5H), while SENP5 inhibited the SUMOylation of USP48 protein (Fig. 5I and J)."

38572092

RELA affects USP

| 1

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

---

➶

sparser

"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

NAMPT affects USP48

| 1

NAMPT acetylates USP48. 1 / 1

| 1

---

➶

sparser

"To further investigate its activity in tumorigenesis, deacetylase sirtuin 1 (Sirt1) was shown to interact with USP31 by co-immunoprecipitation and blocking the function of Sirt1 by knockdown or the inhibitor nicotinamide could increase the acetylation of USP31."

34184746

N -adenosine-methyltransferase subunit affects USP48

| 1

N -adenosine-methyltransferase subunit activates USP48. 1 / 1

| 1

---

➶

reach

"For instance, it has been shown that methyltransferase 14, N -adenosine-methyltransferase subunit (METTL14) upregulates ubiquitin specific peptidase 48 to alleviate liver cancer by regulating Sirtuin 6 stability (4)."

38426536

Mrgprx1 affects USP48

| 1

USP48 binds Mrgprx1. 1 / 1

| 1

---

➶

reach

"USP48 and MrgC interactions were studied by immunoprecipitation."

36864656

MDC1 affects USP48

| 1

USP48 binds MDC1. 1 / 1

| 1

---

➶

sparser

"On the other hand, the five most frequently selected pairs by the agnostic k-TSPs were MDC1-DECR1 (n = 75), MDC1-USP31 (n = 50), CPSF4-RPP40 (n = 43), CHSY1-NIF3L1 (n = 41), and SAC3D1-RPP40 (n = 37) ( xref B)."

36852282

MAP3K7 affects USP48

| 1

USP48 binds MAP3K7. 1 / 1

| 1

---

➶

reach

"Through deubiquitination, USP48 interacts with and stabilizes TAK1, leading to the inhibition of TAK1-triggered NF-κB activation and effectively suppresses CRC tumorigenesis."

39971179

IC 50 affects USP48

| 1

IC 50 inhibits USP48. 1 / 1

| 1

---

➶

reach

"The IC 50 concentrations of the new compounds to inhibit USP48 were determined in a deubiquitinylase activity assay by measuring the fluorescence intensity using tetra-ubiquitin rhodamine110 as substrate."

37196427

Glioma affects USP48

| 1

Glioma activates USP48. 1 / 1

| 1

---

➶

reach

"Interestingly, USP48 is transcriptionally activated by Gli1 in glioma cells, thus forms a positive feedback loop to regulate Hh signaling [65]."

| PMC

GSK3 affects USP48

| 1

GSK3 phosphorylates USP48. 1 / 1

| 1

---

➶

reach

"We have shown that GSK3β phosphorylates USP48, ultimately resulting increases in deubiquitinase activity (S. Li et al., 2018)."

33400290

GPX4 affects USP48

| 1

GPX4 binds USP48. 1 / 1

| 1

---

➶

sparser

"Furthermore, GPX4 protein specifically binds the deubiquitinase USP31, but not other deubiquitinases such as CYLD, USP1, USP14, USP20, USP30, USP38, UCHL1, UCHL3, and UCHL5."

37011699

F3 affects USP48

| 1

USP48 binds F3. 1 / 1

| 1

---

➶

sparser

"USP31 could serve as a potential biomarker for predicting both prognosis and immune responses, revealing its potential mechanisms of TF-USP31 mRNA networks in ccRCC."

37699648

EIF3C affects USP48

| 1

USP48 binds EIF3C. 1 / 1

| 1

---

➶

sparser

"PKD1L3 and more pronouncedly USP31 can interact with eIF3c."

40188851

DUSP3 affects USP48

| 1

DUSP3 binds USP48. 1 / 1

| 1

---

➶

sparser

"DNA sequences encoding the following residues from each USP were cloned into a pET-21b vector using Gibson Assembly 45 : USP4-DUSP, 8–129; USP15-DUSP, 1–125; USP11-DUSP, 71–191; USP20-DUSP1, 687–780; [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

34666042

DUSP1 affects USP48

| 1

DUSP1 binds USP48. 1 / 1

| 1

---

➶

sparser

"DNA sequences encoding the following residues from each USP were cloned into a pET-21b vector using Gibson Assembly 45 : USP4-DUSP, 8–129; USP15-DUSP, 1–125; USP11-DUSP, 71–191; USP20-DUSP1, 687–780; [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

34666042

CSN1S1 affects USP48

| 1

USP48 binds CSN1S1. 1 / 1

| 1

---

➶

reach

"It was recently reported that the deubiquitinylase ubiquitin-specific protease 48 (USP48) interacts with constitutive photomorphogenesis 9 signalosome subunit 1 (CSN1) to stabilize RelA by deubiquitin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37230895

COPS5 affects USP48

| 1

USP48 binds COPS5. 1 / 1

| 1

---

➶

sparser

"A recent study showed that USP48 associates with the COP9 signalosome complex and promotes the nuclear accumulation of NF-κB RelA through its DUB activity, trimming K48-linked ubiquitin chains xref ."

28233861

CASP3 affects USP48

| 1

CASP3 activates USP48. 1 / 1

| 1

---

➶

reach

"Our observations that endogenous p65 level is required for normal synapse formation but USP48 overexpression strikingly inhibits synapse formation in a p65-dependent manner can be explained by USP48-dependent up-regulation of a subset of NF-κB target genes, including proBDNF and Caspase-3."

37781625

BMAL1 affects USP48

| 1

USP48 binds BMAL1. 1 / 1

| 1

---

➶

sparser

"We then validated the binding of Bmal1 to the Usp31 promoter region."

38342927

BLNK affects USP48

| 1

USP48 binds USP, RELA, REL, and BLNK. 1 / 1

| 1

---

➶

sparser

"Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA."

30628021

Atrial Fibrillation affects GPR88, HPCAL1, SWAP70, TBCD, TMEM201, and USP48

| 1

TMEM201 binds TBCD, SWAP70, Atrial Fibrillation, USP48, HPCAL1, and GPR88. 1 / 1

| 1

---

➶

sparser

"However, no previous studies have reported on the association of TMEM201, C1orf43, ANKRD31, TBCD, SWAP70, AF131216.1, USP48, HPCAL1, GPR88 or VSTM2A and LACA."

31853300

ACVRL1 affects USP48

| 1

ACVRL1 activates USP48. 1 / 1

| 1

---

➶

reach

"These effects were also observed with the use of chemotherapy drugs such as HHT, Ara-C, and ATRA, which induced the cleavage of USP48, thereby enhancing drug-induced apoptosis."

39878157