IndraLab

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ADRM1 activates UCHL5. 50 / 67
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"Consistent with our previous report that hRpn13 activates Uch37, the Uch37-hRpn13 complex reacts with UbVS more rapidly than Uch37 alone ( Figure 3 A)."
18922472
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"We further demonstrated that the carboxyl-terminal tail of Uch37 is auto-inhibitory and that hRpn13 activates the Uch37 deubiquitinating activity through interactions with this tail domain."
18922472
sparser
"Furthermore, ADRM1 activates the deubiquitinase UCH37 and avoids its auto-inhibition."
31798765
sparser
"However, this mutant was only marginally activated by the addition of RPN13 DEU (2.7-fold instead of 7-fold in WT), indicating that UCH-L5 activation by RPN13 DEU requires an intact CL ( xref F; xref and xref )."
25702870
sparser
"Stimulation of deubiquitylating activity can now be added to this list of proteasomal functions, but neither ATPase nor proteolytic function of the proteasome is required, as Rpn13 alone can activate Uch37."
18922460
sparser
"Their interaction with ubiquitin is not essential for RPN13 activation of UCH37 for ubiquitin-AMC, as their mutation to alanine produced a 2.5-fold reduction ( xref ) or negligible effect ( xref ); wild-type RPN13 increases this activity 8-fold ( xref ; xref )."
25747657
sparser
"RPN13 and INO80G have opposing effects on UCH37; RPN13 activates UCH37 toward model mono-Ub substrates and INO80G acts as an inhibitor."
29698671
eidos
"Rpn13 , the proteasomal receptor for Uch37 in the proteasome 19S regulatory particle , can activate UCH37 by disrupting dimerization.9 USP14 binds to the regulatory particle Rpn1 to release its catalytic USP domain and polyubiquitin chains of substrate protein.10 Overexpression of Rpn13 or Rpn1 upregulated the COPS5 protein levels and downregulated the p53 protein levels ( Supplementary Fig. S2p ) ."
32257396
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"Ubiquitin receptors play an integral role in substrate capture and apparently contribute to ubiquitin chain deconjugation, as Rpn13 binds and activates deubiquitinating enzyme Uch37 ( xref ; xref ; xref )."
19683493
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"This relocation simultaneously precludes Trp36 availability for ubiquitin binding and impedes the formation of the intricate polar interaction network in the ULD anchor that is required for UCH-L5 activation by RPN13 DEU ( xref C)."
25702870
eidos
"Likewise , while RPN13 promotes UCH37 activity , an additional DUB enzyme USP14 also plays an important role in deubiquitinating substrate proteins , thus potentially explaining the tolerability of systemic administration of RPN13 inhibitors ."
31940398
sparser
"The findings help to understand the mechanism of Uch37 auto-inhibition clearly and shed light on the activation of Uch37 by Rpn13."
24752541
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"We next tested whether RA190 affects hRpn13 activation of Uch37."
28598414
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"HRpn13 activates Uch37 catalytic activity XREF_BIBR XREF_BIBR and recent crystal structures of the Rpn13 DEUBAD -Uch37 complex suggest that the DEUBAD domain promotes accessibility of the Uch37 active site to ubiquitin XREF_BIBR XREF_BIBR XREF_BIBR."
28598414
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"The essential cysteine protease UCH-L5 is activated by proteasome ubiquitin receptor RPN13 (ADRM1) or inhibited by chromatin remodeling complex component INO80 (NFRKB) [ xref ]."
29371935
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"For example, it is not clear how hRpn13 activates Uch37, but it is possible that its strong ubiquitin binding affinity contributes by increasing Uch37 's affinity for its substrates when in the hRpn13 complex and by helping to orient neighboring ubiquitin moieties in a configuration that is optimal for hydrolysis."
20471946
sparser
"To gain a clear understanding of the auto-inhibition mechanism of Uch37 and the Uch37 activation by Rpn13, we investigated the Uch37-Rpn13 complex using a combination of mutagenesis, biochemical, NMR, and SAXS analyses."
24752541
sparser
"These findings suggest that Rpn13 activates Uch37 in the proteasome context and not as a free Uch37/Rpn13 complex ( xref , xref , xref )."
29652515
sparser
"Rpn13 activated Uch37 by forming a 1:1 stoichiometric complex in which the active site of Uch37 was accessible to Ub."
24752541
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"Following binding, Adrm1 relieves UCH37 autoinhibition."
20302916
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"Interestingly, addition of exogenous recombinant hRpn13 to hINO80 caused a marked activation of Uch37, both in UbAMC hydrolysis and in UbVS reactivity."
18922472
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"However, the mechanism by which Rpn13 activates Uch37 is not known."
24752541
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"For a long time, the premise was that the proteasomal subunit RPN13 stimulates the ability of UCH37 to trim the distal end of K48 chains, thereby rescuing proteins prematurely sent to the proteasome for degradation."
33813043
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"Furthermore, ADRM1 activates the deubiquitinase UCH37 and avoids its auto-inhibition."
31798765
sparser
"Thus, hRpn13 activates hINO80-associated Uch37 without displacing it from the hINO80 complex, and activation is a consequence of transient interactions between Uch37 and hRpn13."
18922472
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"A mechanism for the activation of Uch37 by Rpn13 is discussed."
24752541
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"Interestingly, addition of exogenous recombinant hRpn13 to hINO80 caused a marked activation of Uch37, both in UbAMC hydrolysis and in UbVS reactivity (XREF_FIG)."
18922472
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"For example, it is not clear how hRpn13 activates Uch37, but it is possible that its strong ubiquitin-binding affinity contributes by increasing Uch37’s affinity for its substrates when in the hRpn13 complex and by helping to orient neighboring ubiquitin moieties in a configuration that is optimal for hydrolysis."
20471946
sparser
"It has been proved that UCH37 can be activated by proteasome ubiqutin chain receptor Rpn13 and incorporation into the 19S complex."
23725108
sparser
"RPN13 can activate UCH37 by disrupting dimerization, although physiologically relevant activation likely results from stabilization of a surface competent for ubiquitin binding and modulation of the active-site crossover loop."
25702872
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"UCH37 is activated by the proteasomal subunit ADRM1 (also known as RPN13) [XREF_BIBR]."
28881649
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"Uch37 is contributed to the proteasome by hRpn13."
28598414
sparser
"Therefore, it appears that Rpn13 can transiently activate Uch37 in a “hit-and-run” manner without disrupting its association with INO80."
18922460
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"Similarly, UCH37, the human homolog of S. pombe Uch2, is activated by Rpn13, another proteasomal base subunit xref – xref ."
20838651
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"Adrm1 also recruits and activates UCH37, a deubiqitinating enzyme ( xref )."
24910440
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"Interestingly, UCHL5 is activated by the proteasome subunit RPN13 and inhibited by the INO80G subunit ."
34326324
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"Following binding, Adrm1 relieves Uch37 autoinhibition, accelerating the hydrolysis of ubiquitin-7-amido-4-methylcoumarin (ubiquitin-AMC)."
16906146
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"Uch37 was activated by Adrm1 to form Uch37–Adrm1 complex, exhibiting 12-fold higher activity than Uch37 alone ( xref )."
30177931
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"Previous studies indicate that loss of full-length hRpn13 causes corresponding reduction of UCHL5."
32631902
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"And hRpn13 activates hINO80-associated UCH37 without displacing it from the hINO80 complex."
20302916
sparser
"UCH37 is activated by the proteasomal subunit ADRM1 (also known as RPN13) [ xref ]."
28881649
sparser
"Additionally, the expression of a mutant Rpn13 protein that only weakly activates Uch37 on top of the knockdown of wild-type Rpn13 also did not recapitulate the effects of KDT-11 ( xref )."
32857986
sparser
"We further demonstrated that the carboxyl-terminal tail of Uch37 is auto-inhibitory and that hRpn13 activates the Uch37 deubiquitinating activity through interactions with this tail domain."
18922472
sparser
"As shown in xref , expression of the Rpn13 double mutant that only poorly activates Uch37 had no significant effect on viability relative to cells in which wild-type Rpn13 was expressed or to cells in which Rpn13 had not been knocked down at all."
32857986
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"UCHL5 gets activated by binding of ADRM1, which interacts with the C-terminal tail of UCHL5, a region that is different from the UCH catalytic domain [33,141]."
32455657
sparser
"Using a combination of mutagenesis, biochemical, and small-angle X-ray scattering (SAXS) techniques, we demonstrated that Rpn13 activated the auto-inhibited Uch37 by de-oligomerizing it and sequestering it to form a 1:1 stoichiometric complex."
24752541
sparser
"This result is consistent with the inference derived from the biophysical characterization of the Uch37-Rpn13C complex that Rpn13 activates Uch37 through its interaction with the C-terminal domain of Uch37, particularly the KEKE motif."
24752541
sparser
"Consistent with our previous report that hRpn13 activates Uch37, the Uch37-hRpn13 complex reacts with UbVS more rapidly than Uch37 alone ( xref )."
18922472
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"We next tested whether RA190 affects hRpn13 activation of Uch37."
28598414
sparser
"There are likely other factors that contribute to the activation of Uch37 by Rpn13."
24752541