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USP12 binds WDR48. 66 / 87
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"Furthermore, forced USP12 expression significantly potentiated the protein stability of PPM1B (Supplementary Fig. 3d), and the knockdown of WDR48, a binding partner of USP12 that was reported to contribute to USP12 deubiquitinase activity , suppressed PPM1B expression (Supplementary Fig. 3e)."
34381028
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"Here, we report the crystal structure of the USP12-Ub and UAF1 complex at a resolution of 2.8 A and of UAF1 at 2.3 A."
27650958
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"In this regard, it has been reported that, besides USP1, UAF1 also binds and regulates the activity of two other DUBs, namely USP12 and USP46 XREF_BIBR."
22701671
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"XREF_BIBR Notably, a recent study that screened a panel with 22 deubiquitinating enzymes in vitro showed that galeterone inhibits the enzymatic activity of USP12 and also binds directly to the USP12 and USP12 and UAF1 complexes, which dephosphorylate AKT."
27486306
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"As stated earlier, UAF1 interacts with two other USPs, USP12 and USP46."
23797609
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"Interestingly, the addition of WDR20 to the USP12 and UAF1 complex further increased USP12 's DUB activity."
23797609
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"USP1-associated factor 1 (UAF1), which is also called WD repeat-containing protein 48, can bind USP1, USP12, and USP46 and stimulate the activity of these ubiquitin-specific proteases (USPs) (6)."
36988464
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"The UAF1/USP12 complex deubiquitinates PHLPP1 and suppresses the proliferation of tumor cells (41)."
36988464
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"The nucleocytoplasmic distribution of YFP-USP12 “NES”m was identical to that of YFP-USP12 in HeLa cells ( Fig. 6 c), further supporting our view that the motif 77 KESLLTCLADLFHSI 91 is not a direct de[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In C. elegans, USP46 and USP12 both bind to USP1 associated factor 1 (UAF1 and WDR48) and the binding dramatically enhances the activity of USP12 and USP46."
26077708
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"The purified USP12-WDR48 complex was incubated with WDR20 overnight to form the ternary DUB complex that was purified by size-exclusion chromatography."
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"WDR20 preserves and regulates the activity of the USP12-UAF1 deubiquitinating enzyme complex ( xref )."
34779504
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"We then show that in solution USP12 can bind to a second molecule UAF1, but with lower affinity."
27650958
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"The UAF1-USP12 complex was found able to enhance NLRP3 and inflammatory factor (including IL-1β, TNF, and IL-6) production by inhibiting p65 ubiquitination degradation and promoting NF-κB activation."
37752518
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"A study of enzymatic properties of the USP family suggests that the USP12-UAF1 complex is able to cleave all types of chains (except linear) and could theoretically hydrolyze the Lys-29-linked chains formed on Notch by virtue of Itch/AIP4 E3 ubiquitin ligase activity [104–106]."
37752518
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"USP12 binds to Uaf-1 and WDR20 to form a complex to deubiquitinate AR, thereby increasing AR protein stability and transcriptional activity, while the depletion of WDR20 and Uaf-1 displays the opposite effect."
37752518
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"In line with these observed dual binding states, we show here that USP12 and UAF1 complex has 1:2 stoichiometry in solution, with a two-step binding at 4nM and 325nM respectively."
27650958
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"The scaffold protein UAF1 forms a complex with USP1, USP12, and USP46 that is essential for their activity."
36798153
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"The UAF1-USP12 complex has been implicated in sustaining pY701-STAT1 by binding to CREB-binding protein (CBP) and preventing acetylation of pY701-STAT1 and subsequent dephosphorylation by protein tyrosine phosphatase non-receptor type 1 (PTPN2) [64]."
36798153
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"We then show that in solution USP12 can bind to a second molecule UAF1, but with lower affinity."
27650958
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"UAF1 binds USP12 in two distinct steps with different affinities."
27650958
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"Since the conformational change as well as the presence of two UAF1 interfaces seems to be conserved between USP46 and USP12, we wondered what stoichiometry the USP12 and UAF1 complex has in solution."
27650958
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"3.3 UAF1 binds USP12 in two distinct steps with different affinities."
27650958
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"3.2 The USP12 and UAF1 complex has 1:2 stoichiometry."
27650958
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"The UAF1-USP12 complex has been implicated in sustaining pY701-STAT1 by binding to CREB-binding protein (CBP) and preventing acetylation of pY701-STAT1 and subsequent dephosphorylation by protein tyrosine phosphatase non-receptor type 1 (PTPN2) [ xref ]."
36798153
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"The second binding of UAF1 to USP12 does not seem to play a role in the activation of USP12 on a minimal substrate."
27650958
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"The second binding of UAF1 to USP12 does not seem to play a role in the activation of USP12 on a minimal substrate."
27650958
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"WDR48, a WD40 repeat containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity."
21183687
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"A defining feature of WDR20‐dependent activation is that it is necessary for the ability of USP12 to cleave a peptide substrate, Leu‐Arg‐Gly‐Gly (LRGG)‐AMC, since USP12‐UAF1 alone cannot cleave such a substrate (Li et al , xref )."
33619839
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"The partial overlap of the binding interfaces and the high affinity of WDR20 suggests that WDR20 binding to USP12 and UAF1 can either prevent binding of the second UAF1 molecule or it can actively compete out UAF1 if it is bound to the USP12 and UAF1 complex."
27650958
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"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1 associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [XREF_BIBR]."
29386062
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"UAF1 also interacts with DUBs USP12 and USP46 (Garcia-Santisteban et al., 2013) and, thus, both genes also could be involved in senescence."
27160904
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"In addition to binding viral E1, UAF1 interacts with three deubiquitinating enzymes, USP1, USP12, and USP46, leading to formation of a ternary complex on the viral origin, consisting of E1, UAF1, and any one of the three DUBs [XREF_BIBR]."
25254385
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"This latter possibility is surprising given that USP12 and 46 also bind WDR48, but lack this insertion."
26388029
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"Usp12, Uaf-1 and WDR20 form a complex acting within a positive feedback loop in PC cells."
26462181
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"Results confirmed the interaction between endogenous Usp12, Uaf-1 and WDR20 in PC cells."
26462181
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"Reciprocal IP-MS/MS suggests the existence of multiple distinct Dub complexes in which USP12 (or USP46) interacts with WDR48, WDR20 (or DMWD), and PHLPP (or PHLPPL) (XREF_FIG, XREF_SUPPLEMENTARY)."
19615732
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"The scaffold protein UAF1 forms a complex with USP1, USP12, and USP46 that is essential for their activity."
37289831
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"As both Uaf-1 and WDR20 interact with Usp12 we hypothesised that Uaf-1 and WDR20 would also be found in a complex with AR."
26462181
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"We have previously demonstrated that Usp12 and Uaf -1 complex increases AR transcriptional activity."
26462181
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"The UAF1-USP12 complex was found able to enhance NLRP3 and inflammatory factor (including IL-1β, TNF, and IL-6) production by inhibiting p65 ubiquitination degradation and promoting NF-κB activation."
37752518
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"The crystal structures of USP1-UAF1 reveal plasticity in USP1 and key differences to USP12-UAF1 and USP46-UAF1, two related proteases."
33795880
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"Researchers found that ML323, which is a novel NLRP3 inflammatory microsome inhibitor, can specifically inhibit the UAF1/USP1 but not the UAF1-USP12 and UAF1-USP46 complexes [ xref , xref ]."
37752518
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"Structural Comparison of Free and UAF1-bound USP12."
27373336
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"Despite a potential salt bridge and a small number of van der Waal interactions between the two β-propellers, UAF1 binding to USP12 has little effect on the association of WDR20 with the enzyme ( xref )."
27373336
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"All mutants impaired UAF1 and USP12 complex formation (XREF_FIG and XREF_SUPPLEMENTARY)."
27373336
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"Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far away from its catalytic center."
27373336
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"Different from the UAF1-USP46 ~ Ub structure, the previously predicted C-terminal SUMO like domain of UAF1 is clearly resolved in the UAF1 and USP12 complex, in addition to the N-terminal WD40-repeat domain and a central ancillary domain (XREF_FIG, XREF_FIG, XREF_FIG, XREF_SUPPLEMENTARY)."
27373336
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"Fifty percent of inhibition of the closely related USP12–UAF1 and USP46–UAF1 complexes only occurred at 10 μmol/L compared with USP1-UAF1 IC 50 of 4.1 nmol/L, reflecting a >2,000-fold selectivity."
36228090
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"In the inflammatory response, the UAF1-USP12 complex removes K48-linked ubiquitination of the NF-κB subunit p65 and enhances its expression, activating NF-κB signaling and thus promoting NLRP3 transcription."
37752518
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"By contrast, a comparison between the free and UAF1 bound USP12 structures without a suicidal Ub unveils a concatenation of conformational differences spreading across the protein."
27373336
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"In stark contrast, the PK Loop in the UAF1 and USP12 complex structure appears to adopt a flexible structure as evidenced by the absence of its electron density."
27373336
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"To confirm that these structural differences of USP12 are associated with UAF1 binding but not crystal packing or resolution limit, we crystallized the UAF1 and USP12 complex in another space group (C2) and determined its structure at 2.3 A resolution."
27373336
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"In the free USP12 structure and in the F222 space group structure of the UAF1 and USP12 complex, this loop is excluded from the catalytic cleft by BL1 and BL2."
27373336
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"Despite a potential salt bridge and a small number of van der Waal interactions between the two beta-propellers, UAF1 binding to USP12 has little effect on the association of WDR20 with the enzyme (XREF_SUPPLEMENTARY)."
27373336
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"Binding of WDR20 to the UAF1 and USP12 complex induces multiple structural changes in the enzyme, converting it into a compact form similar to Ub bound USP46."
27373336
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"Overall, the UAF1, USP12, and WDR20 complex is distinguished from the two free USP12 structures and the two UAF1 and USP12 complex structures by the apparent stabilization of most flexible structural elements found in the DUB enzyme."
27373336
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"In the two UAF1 and USP12 complex structures, UAF1 binding appears to induce BL1 destabilization via a chain of conformational changes, whereas the WDR20-USP12 interaction seems to overwrite the allosteric effect of UAF1 by re-stabilizing the loop."
27373336
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"Of notice, even though BL1 of USP12 is completely collapsed in our UAF1 and USP12 complex structures, Ub binding is expected to stabilize it via substrate induced fit, as seen in other USPs and the Ub conjugated USP46 structures."
27373336
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"Although BL1 is destabilized in the crystal structures of the UAF1 and USP12 complex, it is expected to adopt a productive conformation upon substrate binding and play an important role in adjusting the topology of the Ub tail by fine tuning its preceding region."
27373336
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"Structural Comparison of Free and UAF1 bound USP12."
27373336
sparser
"A study of enzymatic properties of the USP family suggests that the USP12-UAF1 complex is able to cleave all types of chains (except linear) and could theoretically hydrolyze the Lys-29-linked chains formed on Notch by virtue of Itch/AIP4 E3 ubiquitin ligase activity [ xref – xref ]."
37752518
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"UAF1 also binds and activates two other DUBs, USP12 and USP46 (19), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner (20, 21)."
30456385
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"In the UAF1 and USP12 complex structure, this aromatic residue is dislodged from the pocket but tucked underneath the Ring finger between the side chains of Arg245 and Lys247 (XREF_FIG)."
27373336
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"Recently, our work led to the identification of the deubiquitinating complex USP12 and UAF1, which is recruited by Itch to non activated Notch and allows Notch deubiquitination, probably before its entry into the intraluminal vesicles of the MVBs [XREF_BIBR]."
23519106
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"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity."
27880911