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BRCC3 deubiquitinates NLRP3. 55 / 56
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"BRCC3 deubiquitinates NLRP3 LRR domain and positively regulates NLRP3 inflammasome activation [70]."
37047097
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"For example, NLRP3 inflammasome activation requires ATP-mediated deubiquitination of NLRP3 by BRCA1/BRCA2-Containing Complex Subunit 3 (BRRC3) but is inhibited by interferon (IFN)-γ-induced nitrosylation (1, 31–34)."
36524121
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"Finally, they showed that phosphorylation of S198 by JNK1 allows for de-ubiquitylation of NLRP3 by BRCC3, an essential step for NLRP3 inflammasome activation.Unpublished data from our laboratory have confirmed that the S198D mutant protein drives stronger inflammasome activation compared to WT NLRP3 (ASC speck formation, caspase-1 cleavage) based on a reconstitution assay related to that published by Song et al. (39)."
38022631
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"Moreover, BRCC3 knockdown induced ubiquitination of Flag-NLRP3 in NG5 cells and of endogenous NLRP3 in LPS primed inflammatory peritoneal macrophages."
23246432
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"NLRP3 is rapidly deubiquitylated by BRCC3 upon exposure of cells to LPS and this is required for its full activation [ 46 • ,47 • ]."
25461570
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"A subsequent study identified that the deubiquitinating enzyme, BRCC3, mediates the deubiquitination of NLRP3 [27]."
32545355
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"Increased JNK1 signaling led to NLRP3 deubiquitylation and activation by the deubiquitinase BRCC3 ( BRCA1/BRCA2 -containing complex subunit 3)."
37781816
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"Knockdown of the deubiquitinase BRCC3 increases NLRP3 ubiquitination and inhibits inflammasome activity (25), opposite of our observed phenotype with STAMBP knockout."
33253913
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"NLRP3 deubiquitylation is mediated by the K63 specific deubiquitinase BRCC3."
23702978
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"Altogether, these results demonstrate that BRCC3 mediates the deubiquitination of the LRR domain of NLRP3, an important regulatory mechanism in the activation of NLRP3 inflammasome by its cognate stim[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23246432
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"To identify the DUB associated with NALP7, we over-expressed plasmids expressing several candidate DUBs including BRCC3, which deubiquitinates NALP3, COPS5, STAMBPL1, USP7 and the endosome associated DUBs, STAMBP and USP8."
28492230
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"The K-63-specific deubiquitinating enzyme BRCC3 mediates the deubiquitylation of NLRP3, which has recently been shown to occur in response to pattern recognition receptor stimulation [XREF_BIBR]."
29120406
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"For example, breast cancer 1 (BRCA1)/breast cancer 2 (BRCA2) and containing complex subunit 3 (BRCC3) deubiquitinates NLRP3, and pharmaceutical inhibition of DUBs restricts inflammasome activation [XREF_BIBR, XREF_BIBR, XREF_BIBR], whereas E3 ubiquitin ligases LUBAC and TRIM33 promote inflammasome assembly [XREF_BIBR, XREF_BIBR]."
27783058
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"In turn, the accumulation of cholesterol in the ER activates the inositol triphosphate-3 receptor, CaMKII/JNK, and induces NLRP3 deubiquitylation by BRCC3."
38522750
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"The deubiquitination of NLRP3 by the BRCC3 complex is required for NLRP3 inflammasome activation XREF_BIBR XREF_BIBR XREF_BIBR."
27929086
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"Our findings indicate that cholesterol trafficking from the plasma membrane (PM) to the endoplasmic reticulum (ER), via Aster-B leads to the activation of calcium/calmodulin-dependent kinase II (CaMKII) and JNK and subsequent NLRP3 deubiquitylation by BRCC3 to promote NLRP3 inflammasome activation."
38522750
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"By screening a deubiquitinating enzyme (DUB) library, they recognized that BRCC3 (BRCA1, BRCA2, and containing complex subunit 3) deubiquitinates the LRR domain of NLRP3, which then proceeds NLRP3 activation 59."
30755589
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"BRCC3 inhibition promotes NLRP3 ubiquitination and blocks inflammasome assembly but does not target NLRP3 for degradation."
30288079
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"JNK1 signaling augmentation leads to NLRP3 deubiquitination and activation by the deubiquitinase BRCC3 (BRCA1/BRCA2-containing complex subunit 3) (Yalcinkaya et al. 2023)."
40080209
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"Besides phosphorylation, the deubiquitinating enzyme BRCA1/BRCA2-containing complex subunit 3 (BRCC3) promotes an inflammasome activation by deubiquitinating NLRP3 at its LRR domain153."
32550001
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"In addition, the priming step also leads to deubiquitination of NLRP3 by the Lys-63-specific deubiquitinase BRCC3 (Py et al., 2013), allowing subsequent oligomerization.The second signal can vary widely between different cell types and different inflammasome types."
36685206
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"Cholesterol trafficking from PM to ER, via Aster-B leads to activation of CaMKII/JNK and subsequent NLRP3 deubiquitylation by BRCC3 to promote NLRP3 inflammasome activation."
38522750
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"BRCC3, a JAMM domain containing Zn2+ metalloprotease, promotes NLRP3 deubiquitination during priming and regulates NLRP3 activation [XREF_BIBR]."
27669650
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"Here, we initially reported that the pathogenesis of PD mediated by neuronal NLRP3 inflammasome was associated with deubiquitinase BRCC3.Murine Lys-63-specific deubiquitinase BRCC3 and its human homol[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31787240
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"For instance, ubiquitination of NLRP3 by FBXL12, TRIM1, ARIH2 or the dopamine induced E3 ligase MARCH7 promotes the proteasomal degradation of NLRP3 in resting macrophages, whereas deubiquitylation of NLRP3 LRR domain on K63 by BRCC3 triggers ASC oligomerization and inflammasome activation (XREF_FIG)."
33716981
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"TLR and ROS signaling can increase the levels of NLRP3 via BRCA1/BRCA2-containing complex subunit 3 (BRCC3) which mediates deubiquitination of the LRR domain of NLRP3 and such modification is essential for its activation (Py et al., 2013)."
30405440
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"Py et al. found that BRCC3 promotes NLRP3 inflammasome activation by deubiquitinating the LRR domain of NLRP3 50."
25762778
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"Further investigations revealed that silencing BRCC3 increased the ubiquitination of NLRP3, whereas overexpressing BRCC3 decreased it."
39642564
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"It has been reported that deubiquitination of NLRP3, mediated by a DUB BRCC3, is a required step for activation of the NLRP3 inflammasome."
26620909
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"A previous study has demonstrated that BRCC3, a K63 specific deubiquitinase, enhances NLRP3 inflammasome activity by deubiquitinating NLRP3 35."
30315153
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"The mechanism behind this observation is likely TLR4-MyD88-dependent deubiquitination of NLRP3 by BRCC3, which is essential for its activation."
24367371
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"In addition, NLRP3-NEK7 binding is also essential for NLRP3 deubiquitination by BRCC3 and subsequently inflammasome assembly, with NLRP3 phosphomimetic mutants showing enhanced ubiquitination and degradation than wildtype NLRP3."
34615873
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"The deubiquitylation of NLRP3 required as an activating step is mediated by BRCC3, however there is no evidence to support gain of function of BRCC3 leading to constitutively activated NLRP3 [22] ."
25814341
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"Recently, BRCC3 in the cytosol has been reported to promote the inflammasome activation by deubiquitinating NLRP3 in LPS primed macrophages [XREF_BIBR]."
25337721
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"NLRP3 deubiquitination is mediated by BRCC3, a member of JAMM domain containing Zn 2+ metalloprotease deubiquitinating enzyme family, therefore providing a novel therapeutic target for IL-1beta-associated inflammatory diseases."
24054327
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"For example, ATP and TLR-4 may activate the deubiquitination of NLRP3 in macrophages (41) by the enzyme BRCA1/BRCA2-containing complex subunit 3 (BRCC3) (42) and c-Jun N-terminal kinase (JNK1)-mediated NLRP3 S194 phosphorylation may induce NLRP3 deubiquitination with a subsequent inflammasome assembly (43)."
38020086
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"BRCA1/BRCA2-containing complex subunit 3 (BRCC3) deubiquitinates NLRP3 and is required for NLRP3 oligomerization and activation (26)."
37651190
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"46 In addition, the loss of interaction between A20 p.(Lys91*) mutant and the BRCC3-containing BRISC complex suggests a further novel NLRP3-regulating function of A20 that is lost in haploinsufficient cells, as BRCC3 deubiquitinates the NLRP3 receptor directly promoting its activation."
30402268
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"A posttranscriptional modification, such as NLRP3 deubiquitination mediated by BRCA1/BRCA2-containing complex subunit 3 (BRCC3), is required for NLRP3 activation (signal 2) [67, 68]."
31687078
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"It has been demonstrated that VDR inhibits the deubiquitination of NLRP3 by BRCC3 (35), which is a deubiquitinase with a crucial role for the post-transcriptional activation of NLRP3 (88)."
37867510
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"BRCA1-BRCA2-containing complex subunit 3 (BRCC3), a deubiquitinating enzyme, can deubiquitinate the NLRP3 LRR domain and promote NLRP3 inflammasome activation [60] ."
35365780
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"For example, NLRP3 is deubiquitinated by Lys-63-specific deubiquitinase BRCC36 (BRCC3) during priming, which facilitates NLRP3 inflammasome activation [12] ."
29452983
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"Song et al. found that NLRP3 S194 phosphorylation promotes its interaction with the deubiquitinase BRCC3, which in turn induces the deubiquitination of NLRP3 and its subsequent activation."
33627128
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"Moreover, a recent report described that R779C, a gain of function mutation of NLRP3, promotes NLRP3 de-ubiquitylation by BRCC3 and JOSD2 to promote NLRP3 activation, which increases the risk of developing Very-early-onset inflammatory bowel disease (VEOIBD), a chronic inflammatory disease of the gastrointestinal tract can happen in early childhood (Zhou et al., 2021)."
35800898
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"For instance, NLRP3 deubiquitinated by Lys-63-specific deubiquitinase BRCC36 during priming is beneficial for NLRP3 inflammasome activation [7] ."
34482265
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"Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3."
36600050
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"For example, the Lys-63-specific deubiquitinase, BRCC36 (BRCC3), promotes NLRP3 deubiquitination and facilitates NLRP3 inflammasome activation during priming [34] ."
30049633
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"It has been demonstrated that BRCC3 promotes NLRP3 deubiquitination by directly binding to NLRP3, thereby favoring NLRP3 oligomerization and activation."
37361896
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"Priming also has a second consequence: the deubiquitination of NLRP3 by BRCC3, which is a prerequisite to NLRP3 inflammasome activation [ 52 ]."
30772258
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"BRCC3 mediates the deubiquitination of the LRR domain of NLRP3, which in turn recruits ASC, activates caspase-1, and releases the proinflammatory cytokine IL-1β, for which ABRO1 binding to the NBD and NACHT domain of NLRP3 is essential [ 78, 79] ."
36148948
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"A variety of NLRP3 inhibitors are in development including those that target the BRCC3/ABRO1 pathway that mediates specific deubiquitination and activation of NLRP3 ."
36337911
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"For example, deubiquitination of the LRR domain of NLRP3 by BRCC3, a JAMM domain containing Zn 2+ metalloprotease deubiquitinating enzyme, leads to activation of the inflammasome."
25879280
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"The deubiquitination of NLRP3 by the BRCC3 complex is required for NLRP3 activation, and the K63 linked ubiquitination of ASC targets the AIM2-ASC inflammasome complex for destruction in autophagosomes."
24958845
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"Moreover, BRCC3 [18], STING [19] and ABRO1 [20] can be activated by NLRP3 agonists, such as ATP, to promote the deubiquitination and sensitivity of NLRP3."
| PMC
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"However, ABRAXAS2- and BRCC3-dependent deubiquitination of NLRP3 also requires an NLRP3 activation stimulus [162,165]."
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