IndraLab
Statements
reach
"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Unpublished data from our laboratory have confirmed that the S198D mutant protein drives stronger inflammasome activation compared to WT NLRP3 (ASC speck formation,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)."
reach
"The authors further suggested that the deubiquitylation of NLRP3 was critical for the inflammasome activation based on the facts that inhibiting BRCC3 could abolish NLRP3 inflammasome activation under a diverse range of classic " activation signals, " including K + efflux, ROS overproduction, and lysosomal destabilization."
reach
"Our collective data supported the requirement of the VDR‐BRCC3 signaling pathway for VD3‐induced inactivation of the NLRP3 inflammasome and subsequent inhibition of hyperinflammation in HBE‐N cells.2.4
VD3 attenuated N protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway in vivo."
reach
"Structural studies indicate that BRCC36 and ABRAXAS2 or ABRO1 form heterodimers, which ensure enzymatic activity and association with additional cofactors including RAP80 and BRCA1 (in the BRCA1-A complex) or the serine hydroxymethyltransferase 2 (SHMT2) (in the BRISC complex) (107, 108, 109)."
reach
"This mechanism is homologous to what has been observed in the ancestral BRCC36-KIAA0157 complex (Zeqiraj et al., 2015) but is distinct from that seen in the COP9 signalosome (CSN) and the proteasome lid, where the position of the scaffold MPN domain differs (Figure S3B) (Lingaraju et al., 2014, Pathare et al., 2014, Worden et al., 2014, Worden et al., 2017)."
reach
"Based on current reports, JAMM subunit interfaces are surprisingly diverse in structure and have a variety of roles including function in : i) the assembly of multisubunit complexes and ii) maintaining the JAMM and MPN+ domain in an active state, as in the BRCC36 and KIAA0157 heterodimer."
reach
"We pursued crystallization of BRCC36-KIAA0157 subcomplexes from different species (H. sapiens, G. gallus, X. tropicalis, D. rerio, C. floridanus and A. thaliana) to determine the structural basis for (1) how KIAA0157 supports the catalytic function of BRCC36, and (2) how super dimerization of the minimally active BRCC36 and KIAA0157 heterodimer is mediated."
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
"These findings identify BRCC as a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage.|Reconstitution of a recombinant four-subunit complex containing BRCA1/BARD1/BRCC45/BRCC36 revealed an enhanced E3 ligase activity compared to that of BRCA1/BARD1 heterodimer"
reach
"The so called BRCA1-A complex comprises RAP80, Abraxas and CCDC98, the deubiquitinase BRCC36, BRCC45 and MERIT40, which are thought to target BRCA1 to IR induced foci through the interaction of RAP80 with polyubiquitin chains such as is thought to occur at histone gamma-H2AX [XREF_BIBR, XREF_BIBR] (see XREF_FIG)."
reach
"The study has demonstrated that BRCC3 depletion prevents the formation of BRCA1 nuclear foci, and subsequently impairs the DNA repair pathway in response to DNA damage by ionizing radiation in breast cancer cells, suggesting that BRCC3 is referred as a potential therapeutic target for breast cancer [XREF_BIBR]."
reach
"Structural studies indicate that BRCC36 and ABRAXAS2 or ABRO1 form heterodimers, which ensure enzymatic activity and association with additional cofactors including RAP80 and BRCA1 (in the BRCA1-A complex) or the serine hydroxymethyltransferase 2 (SHMT2) (in the BRISC complex) (107, 108, 109)."
reach
"This mechanism is homologous to what has been observed in the ancestral BRCC36-KIAA0157 complex (Zeqiraj et al., 2015) but is distinct from that seen in the COP9 signalosome (CSN) and the proteasome lid, where the position of the scaffold MPN domain differs (Figure S3B) (Lingaraju et al., 2014, Pathare et al., 2014, Worden et al., 2014, Worden et al., 2017)."
reach
"Based on current reports, JAMM subunit interfaces are surprisingly diverse in structure and have a variety of roles including function in : i) the assembly of multisubunit complexes and ii) maintaining the JAMM and MPN+ domain in an active state, as in the BRCC36 and KIAA0157 heterodimer."
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
"These findings identify BRCC as a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage.|Reconstitution of a recombinant four-subunit complex containing BRCA1/BARD1/BRCC45/BRCC36 revealed an enhanced E3 ligase activity compared to that of BRCA1/BARD1 heterodimer"
reach
"For example, Pellino2 activates NLRP3 through K63-linked ubiquitination during priming, while HUWE1A1 targets NLRP3, NLRC4, and AIM2 with K27-linked polyubiquitination, both boosting inflammasome assembly and pyroptosis.42, 43, 44Deubiquitylation is also crucial in inflammasome activation, with deubiquitinating enzymes (DUBs) like BRCC36 stimulating NLRP3 inflammasome activity and pyroptosis by reversing ubiquitination.45 USPs, a major DUB family regulating NLRP3 inflammasomes, such as USP9X, USP14, USP7, and USP47, promote NLRP3 activity, cytokine release, and pyroptosis through cleaving ubiquitin chains from NLRP3.46, 47, 48
Phosphorylation."
reach
"In the model, both Ser806 and Tyr861 must be unphosphorylated for NLRP3 to bind NEK7, and NLRP3 must bind NEK7 to allow BRCC36 mediated deubiquitylation of the LRR domain.The phosphorylation of Ser295 has been shown to act as both a positive and negative regulator of NLRP3 activation (
Figure 6
)."
reach
"BRCA1 binds with its BRCT domain to phosphorylated ABRA1, which acts as a scaffold and binds BRCC36 (BRCA1 and BRCA2 containing complex subunit 36, also known as BRCC3), a deubiquitinating enzyme, BRCC45 (BRCA1 and BRCA2 containing complex subunit 45, also known as BRE), and RAP80, which is essential for the recruitment of BRCA1."
reach
"BRCA1 binds with its BRCT domain to phosphorylated ABRA1, which acts as a scaffold and binds BRCC36 (BRCA1 and BRCA2 containing complex subunit 36, also known as BRCC3), a deubiquitinating enzyme, BRCC45 (BRCA1 and BRCA2 containing complex subunit 45, also known as BRE), and RAP80, which is essential for the recruitment of BRCA1."
reach
"Figure 4B shows that BRCC36 overexpression significantly inhibited the degradation of HMGCR in HepG2 and SMMC7721 cells treated with CHX, while HMGCR protein was markedly degraded after depletion of BRCC36 in Hep3B cells treated with CHX.To examine whether BRCC36 blocks the ubiquitination of HMGCR, we detected the ubiquitination level of HMGCR."
reach
"Figure 4B shows that BRCC36 overexpression significantly inhibited the degradation of HMGCR in HepG2 and SMMC7721 cells treated with CHX, while HMGCR protein was markedly degraded after depletion of BRCC36 in Hep3B cells treated with CHX.To examine whether BRCC36 blocks the ubiquitination of HMGCR, we detected the ubiquitination level of HMGCR."
reach
"Figure 4B shows that BRCC36 overexpression significantly inhibited the degradation of HMGCR in HepG2 and SMMC7721 cells treated with CHX, while HMGCR protein was markedly degraded after depletion of BRCC36 in Hep3B cells treated with CHX.To examine whether BRCC36 blocks the ubiquitination of HMGCR, we detected the ubiquitination level of HMGCR."
BRCC3 affects cell population proliferation
|
20
BRCC3 activates cell population proliferation.
|
13
BRCC3 inhibits cell population proliferation.
|
7
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
reach
"Thus, it seems likely that the apparent requirement of BRCC45 for DUB activity of the BRCA1-A complex, but not BRISC, is not due to major structural differences between the two complexes, but merely reflects a specific stabilizing effect of BRCC45 on Abraxas and BRCC36 complexes that is not required by Abro1 and BRCC36."
reach
"The structure of an active core complex comprising twoAbraxas/BRCC36/BRCC45/MERIT40 tetramers determined by negative-stain electron microscopy (EM) reveals a distorted V-shape architecture in which a dimer of Abraxas and BRCC36 heterodimers sits at the base, with BRCC45 and Merit40 pairs occupying each arm."
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
reach
"To examine the interaction between endogenous BRCC3 and ZEB1 in MDA-MB-231 cells, 20 μL of Protein A/G Agarose was mixed with 5 μL of anti-ZEB1 antibody (ab276129; Abcam) or anti-BRCC3 antibody (ab115172; Abcam) and incubated for 2 h at room temperature, after which the supernatant was added and incubated overnight at 4°C. IgG was used as a negative control."
reach
"Thus, it seems likely that the apparent requirement of BRCC45 for DUB activity of the BRCA1-A complex, but not BRISC, is not due to major structural differences between the two complexes, but merely reflects a specific stabilizing effect of BRCC45 on Abraxas and BRCC36 complexes that is not required by Abro1 and BRCC36."
reach
"The structure of an active core complex comprising twoAbraxas/BRCC36/BRCC45/MERIT40 tetramers determined by negative-stain electron microscopy (EM) reveals a distorted V-shape architecture in which a dimer of Abraxas and BRCC36 heterodimers sits at the base, with BRCC45 and Merit40 pairs occupying each arm."
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
BRCC3 affects cell differentiation
|
14
BRCC3 inhibits cell differentiation.
|
8
BRCC3 inhibits cell differentiation. 7 / 7
|
7
Modified BRCC3 inhibits cell differentiation. 1 / 1
|
1
BRCC3 activates cell differentiation.
|
6
BRCC3 affects Neoplasm Invasiveness
|
14
BRCC3 activates Neoplasm Invasiveness.
|
9
BRCC3 inhibits Neoplasm Invasiveness.
|
5
reach
"Therefore, investigating these aspects will provide deeper insights into the involvement of BRCC3 in neuroinflammation and pyroptosis, potentially paving the way for novel therapeutic strategies to mitigate the harmful effects of cerebral I/R injury and improve the neurological outcomes in patients.We aimed to explore the effect of BRCC3 in neuroinflammation and pyroptosis after cerebral I/R injury in mice and the potential mechanism via which BRCC3 activates the NLRP6 inflammasome.3
RESULTS."
BRCC3 affects pyroptosis
|
13
BRCC3 activates pyroptosis.
|
11
BRCC3 activates pyroptosis. 10 / 11
|
11
reach
"Besides, BRCC3 could activate NLRP3 inflammasome-dependent pyroptosis (26), which could then promote tumor progression.In conclusion, UCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which promoted cell proliferation, migration, and inhibited apoptosis."
reach
"50
BRCC36 overexpression upregulates GSDMD expression and induces chronic pyroptosis, both of which deteriorate the tumor microenvironment (TME) over time and accelerate tumor growth, but this needs to be further studied.Furthermore, THL could inhibit the activity of the BRCC36 enzyme, reduce HMGCR protein levels, and suppress tumor growth."
BRCC3 inhibits pyroptosis.
|
2
BRCC3 inhibits pyroptosis. 2 / 2
|
2
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
reach
"For example, HSV-1 ICP0 protein was reported to degrade the host deubiquitinase BRCC36 and further downregulate IFN-I receptor IFNAR1 , and HSV-1 ICP27 protein was found to interfere with STAT-1 activation and hamper the downstream transcription of ISGs (interferon-stimulated genes) ."
reach
"For example, ICP0 can disrupt promyelocytic leukemia nuclear bodies (PML-NBs) through the function of E3 Ub ligase, degrade speckled protein 100 (Sp100) in a RING-finger dependent manner, and degrade the host K63-linkage specific deubiquitinase BRCC36 to antagonize the type I interferon (IFN-1) antiviral response [9]."
BRCC3 affects inflammatory response
|
9
BRCC3 activates inflammatory response.
|
5
BRCC3 inhibits inflammatory response.
|
4
BRCC3 affects Carcinogenesis
|
2
7
BRCC3 activates Carcinogenesis.
|
2
4
BRCC3 activates Carcinogenesis. 6 / 6
|
2
4
reach
"Our findings showed BRCC3 plays a crucial role in facilitating the development and progression of bladder cancer.To reveal the way how BRCC3 promotes carcinogenesis, we analyzed BRCC3-deficient bladder cancer cell lines by RNA-Seq, and the data showed that the NF-κB inflammatory pathway was notably downregulated when BRCC3 was knockout."
BRCC3 inhibits Carcinogenesis.
|
3
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
BRCC3 affects signal transduction
|
8
BRCC3 activates signal transduction.
|
5
BRCC3 inhibits signal transduction.
|
3
BRCC3 affects Neoplasm Metastasis
|
8
BRCC3 inhibits Neoplasm Metastasis.
|
5
BRCC3 activates Neoplasm Metastasis.
|
3
BRCC3 activates Neoplasm Metastasis. 3 / 3
|
3
reach
"Consistent with the idea that dysregulated DNA repair promotes tumorigenesis [60], several studies have reported that aberrant expression of BRCC3 contributes to the progression or metastasis of several carcinomas, including pancreatic cancer [61] and gastric cancer [62] and represents a promising prognostic marker and a potential target in the therapies for these cancer types."
reach
"However, in BRCC36 silenced cells, a large proportion of NuMA aggregates was retained in the peripheral areas distant from the spindle poles (XREF_FIG; 25-30 min), and supernumerary poles were formed, indicating that depletion of BRCC36 decreases the incorporation of NuMA into spindle poles during mitosis, presumably by aberrant dynamic interaction between NuMA and its partner dynein."
BRCC3 affects Cell Survival
|
7
BRCC3 inhibits Cell Survival.
|
3
BRCC3 activates Cell Survival.
|
4
Bisphenol A affects BRCC3
7
|
Bisphenol A decreases the amount of BRCC3.
5
|
Bisphenol A increases the amount of BRCC3.
2
|
BRCC3 affects ferroptosis
|
7
BRCC3 inhibits ferroptosis.
|
5
BRCC3 activates ferroptosis.
|
2
|
7
BRCC3 inhibits epithelial to mesenchymal transition.
|
5
BRCC3 activates epithelial to mesenchymal transition.
|
2
BRCC3 activates epithelial to mesenchymal transition. 2 / 2
|
2
BRCC3 affects chloroethene
|
7
reach
"To examine the interaction between endogenous BRCC3 and ZEB1 in MDA-MB-231 cells, 20 μL of Protein A/G Agarose was mixed with 5 μL of anti-ZEB1 antibody (ab276129; Abcam) or anti-BRCC3 antibody (ab115172; Abcam) and incubated for 2 h at room temperature, after which the supernatant was added and incubated overnight at 4°C. IgG was used as a negative control."
reach
"The TRIM14-USP14-BRCC3 complex inhibits OPTN-mediated autophagic degradation of KDM4D by reducing K63 ubiquitination on KDM4D, thereby removing the H3K9me3 modification from the promoters of IL-12 and IL-23, promoting the expression of the pro-inflammatory cytokines IL-12 and IL-23, and enhancing the inflammatory response [158]."
reach
"Whether these TRIMs are in charge of KDM4D ubiquitination needs further investigation.Collectively, our data provide evidence for the autophagic control of epigenetic regulation in inflammation, as the TRIM14–USP14–BRCC3 complex stabilizes KDM4D and prevents its autophagic degradation in DCs to mediate the pathogenesis of EAE (SI Appendix, Fig. S8)."
reach
"50
BRCC36 overexpression upregulates GSDMD expression and induces chronic pyroptosis, both of which deteriorate the tumor microenvironment (TME) over time and accelerate tumor growth, but this needs to be further studied.Furthermore, THL could inhibit the activity of the BRCC36 enzyme, reduce HMGCR protein levels, and suppress tumor growth."
reach
"Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome, Associated-molecule-with-the-SH3-Domain-of-STAM (AMSH), which regulates ubiquitin dependent sorting of cell-surface receptors, and Brcc36, a K63 specific deubiquitnase of BRCC36 containing isopeptidase complex (BRISC) and BRCA1, BRCA2, and containing complex (BRCC)."
reach
"In addition, a few other mechanisms may also underlie B7H3 mediated chemoresistance : (1) B7H3 induces oxaliplatin resistance by increasing the expression of XRCC1 via PI3K and AKT pathway; (2) B7H3 also enhances cell resistance to chemotherapy by increasing the expression of BRCC3, which antagonizes DNA damage caused by 5-FU; (3) or via the activation of the PI3K and AKT pathway."
BRCC3 affects apoptotic process
|
6
BRCC3 inhibits apoptotic process.
|
4
BRCC3 inhibits apoptotic process. 4 / 4
|
4
reach
"Besides, BRCC3 could activate NLRP3 inflammasome-dependent pyroptosis (26), which could then promote tumor progression.In conclusion, UCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which promoted cell proliferation, migration, and inhibited apoptosis."
BRCC3 activates apoptotic process.
|
2
reach
"The TRIM14-USP14-BRCC3 complex inhibits OPTN-mediated autophagic degradation of KDM4D by reducing K63 ubiquitination on KDM4D, thereby removing the H3K9me3 modification from the promoters of IL-12 and IL-23, promoting the expression of the pro-inflammatory cytokines IL-12 and IL-23, and enhancing the inflammatory response [158]."
reach
"Whether these TRIMs are in charge of KDM4D ubiquitination needs further investigation.Collectively, our data provide evidence for the autophagic control of epigenetic regulation in inflammation, as the TRIM14–USP14–BRCC3 complex stabilizes KDM4D and prevents its autophagic degradation in DCs to mediate the pathogenesis of EAE (SI Appendix, Fig. S8)."
BRCC3 affects TNBC
|
6
BRCC3 affects DNA repair
|
4
BRCC3 activates DNA repair.
|
3
BRCC3 inhibits DNA repair.
|
1
BRCC3 inhibits DNA repair. 1 / 1
|
1
BRCC3 affects DNA Damage
|
6
BRCC3 inhibits DNA Damage.
|
5
BRCC3 inhibits DNA Damage. 5 / 5
|
5
reach
"In addition, a few other mechanisms may also underlie B7H3 mediated chemoresistance : (1) B7H3 induces oxaliplatin resistance by increasing the expression of XRCC1 via PI3K and AKT pathway; (2) B7H3 also enhances cell resistance to chemotherapy by increasing the expression of BRCC3, which antagonizes DNA damage caused by 5-FU; (3) or via the activation of the PI3K and AKT pathway."
BRCC3 activates DNA Damage.
|
1
BRCC3 activates DNA Damage. 1 / 1
|
1
MiR-US25-1 affects BRCC3
|
5
reach
"Subsequently, through a series of comprehensive gain and loss-of-function experiments, we have reaffirmed the positive correlation between BRCC3 protein expression and USP15, confirming the pivotal role of USP15 in modulating the multiplication, invasiveness, and migration of bladder cancer by regulating BRCC3 expression.Subsequently, to assess the interaction between USP15 and BRCC3, we conducted meticulous Co-IP experiments, conclusively demonstrating direct binding between the two proteins."
reach
"The TRIM14-USP14-BRCC3 complex inhibits OPTN-mediated autophagic degradation of KDM4D by reducing K63 ubiquitination on KDM4D, thereby removing the H3K9me3 modification from the promoters of IL-12 and IL-23, promoting the expression of the pro-inflammatory cytokines IL-12 and IL-23, and enhancing the inflammatory response [158]."
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
Hsa-miR-223-5p affects BRCC3
4
|
Hsa-miR-190a-3p affects BRCC3
4
|
reach
"The TRIM14-USP14-BRCC3 complex inhibits OPTN-mediated autophagic degradation of KDM4D by reducing K63 ubiquitination on KDM4D, thereby removing the H3K9me3 modification from the promoters of IL-12 and IL-23, promoting the expression of the pro-inflammatory cytokines IL-12 and IL-23, and enhancing the inflammatory response [158]."
BRCC3 affects temozolomide
|
4
reach
"The TRIM14-USP14-BRCC3 complex inhibits OPTN-mediated autophagic degradation of KDM4D by reducing K63 ubiquitination on KDM4D, thereby removing the H3K9me3 modification from the promoters of IL-12 and IL-23, promoting the expression of the pro-inflammatory cytokines IL-12 and IL-23, and enhancing the inflammatory response [158]."
reach
"At the endogenous level of TAZ (no doxycycline treatment), BRCC3 KD raised the expression of Cyr61, while upon TAZS89A expression, both TAZ target genes are significantly upregulated (Figure 2a), thus confirming the result of the screen.TAZ activity is mainly regulated by post-translational modifications, which affect its protein stability and its cellular localization [2,41]."
reach
"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."
reach
"Priming requires IRAK1 activation and proteasome dependent ERK activation (with downstream MEK1/2 activation), and it involves post-translational modifications including : (i) BRCC3 mediated NLRP3 deubiquitination, (ii) LUBAC mediated ASC ubiquitination, and (iii) SYK- and JNK dependent ASC phosphorylation."
reach
"Priming requires IRAK1 activation and proteasome dependent ERK activation (with downstream MEK1/2 activation), and it involves post-translational modifications including : (i) BRCC3 mediated NLRP3 deubiquitination, (ii) LUBAC mediated ASC ubiquitination, and (iii) SYK- and JNK dependent ASC phosphorylation."
BRCC3 affects Interferon
|
4
BRCC3 deubiquitinates Interferon.
|
3
BRCC3 deubiquitinates Interferon. 3 / 3
|
3
reach
"Dr. Greenberg group from University of Pennsylvania showed that BRCC36 containing deubiquitinating complex BRISC which is also a sister protein complex of nuclear RAP80-BRCA1 complex, deubiquitinates type I interferon receptor (IFNAR1), resulting in its delayed lysosomal dependent degradation."
BRCC3 activates Interferon.
|
1
BRCC3 activates Interferon. 1 / 1
|
1
reach
"Unlike USP2A, the deubiquitinating enzymes BRCC36, USP13, and USP39 positively regulate IFN activities by attenuating the polyubiquitination level of STAT1, and this process is independent of IFN treatment, which suggests divergent functional roles of these DUBs under differential contexts.Additionally, ATXN3 does not affect IFN-I production during viral infection but positively regulates IFNAR1-mediated downstream signaling by targeting HDAC3 (108)."
Si-UCA1 affects BRCC3
|
3
Si-UCA1 decreases the amount of BRCC3.
|
2
reach
"These results meant that the inhibited effects of si-UCA1 on tumor progression were partly attenuated after cotransfection of si-UCA1 and miR-582-5p inhibitors.3.7.2
Simultaneously inhibited the expression of UCA1 and enhanced the expression of BRCC3 in pancreatic cancer cells, and then observed cell proliferation, apoptosis, and metastasis."
Si-UCA1 increases the amount of BRCC3.
|
1
reach
"These results meant that the inhibited effects of si-UCA1 on tumor progression were partly attenuated after cotransfection of si-UCA1 and miR-582-5p inhibitors.3.7.2
Simultaneously inhibited the expression of UCA1 and enhanced the expression of BRCC3 in pancreatic cancer cells, and then observed cell proliferation, apoptosis, and metastasis."
MiR-369-3p affects BRCC3
|
3
LncRNA NEAT1 affects BRCC3
|
3
Hsa-miR-6867-5p affects BRCC3
3
|
Hsa-miR-574-5p affects BRCC3
3
|
Hsa-miR-511-3p affects BRCC3
3
|
Hsa-miR-5011-5p affects BRCC3
3
|
Hsa-miR-3121-5p affects BRCC3
3
|
Hsa-miR-1277-5p affects BRCC3
3
|
Benzo[a]pyrene affects BRCC3
3
|
Benzo[a]pyrene methylates BRCC3.
1
|
Benzo[a]pyrene increases the amount of BRCC3.
1
|
Benzo[a]pyrene decreases the amount of BRCC3.
1
|
sparser
"MERIT40 (BABAM1), as a RAP80-associated protein, is named as an important component of BRISC (Brcc36 isopeptidase complex) and BRCA1 (BReast-CAncer susceptibility gene 1) DNA damage repair complex A. When DNA damage occurs, BABAM1 helps to locate the repair complex to the site of damage, stabilizes the structure of the complex to cause ubiquitination at the site of damage, and trigger cell cycle G2 arrest ( xref ; xref ; xref )."
TMPO-AS1 affects BRCC3
|
2
1
PIO affects BRCC3
|
3
reach
"Our data preliminarily revealed that PIO upregulated BRCC36 expression in the aortic tissues of CKD mice and VSMCs and further elucidated some of the mechanisms by which pioglitazone affects VC; however, our results did not further confirm that BRCC36 was a direct target of PIO via pull-down assays and proteomic microarrays."
NEAT1 affects BRCC3
|
3
reach
"However, the present study did not focus on the effects of NEAT1/miR-204/BRCC3 signals on these forms of regulatory cell death.The present study focused on NLRP3 inflammasome activation-dependent pyroptosis in cardiovascular I/R injury and demonstrated that NEAT1 positively regulated BRCC3 expression and NLRP3 inflammasome activation-dependent pyroptosis by competitively binding with miR-204."
1
1
|
BRCC3 affects interferon receptor
|
3
reach
"Dr. Greenberg group from University of Pennsylvania showed that BRCC36 containing deubiquitinating complex BRISC which is also a sister protein complex of nuclear RAP80-BRCA1 complex, deubiquitinates type I interferon receptor (IFNAR1), resulting in its delayed lysosomal dependent degradation."
BRCC3 affects homologous recombination
|
3
BRCC3 affects cell migration
|
3
BRCC3 affects cell growth
|
2
BRCC3 inhibits cell growth.
|
1
BRCC3 inhibits cell growth. 1 / 2
|
1
BRCC3 activates cell growth.
|
1
BRCC3 activates cell growth. 1 / 1
|
1
BRCC3 affects angiogenesis
|
3
BRCC3 activates angiogenesis.
|
2
BRCC3 inhibits angiogenesis.
|
1
BRCC3 inhibits angiogenesis. 1 / 1
|
1
sparser
"MERIT40 (BABAM1), as a RAP80-associated protein, is named as an important component of BRISC (Brcc36 isopeptidase complex) and BRCA1 (BReast-CAncer susceptibility gene 1) DNA damage repair complex A. When DNA damage occurs, BABAM1 helps to locate the repair complex to the site of damage, stabilizes the structure of the complex to cause ubiquitination at the site of damage, and trigger cell cycle G2 arrest ( xref ; xref ; xref )."
BRCC3 affects E3_Ub_ligase
|
3
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
reach
"Interactions of Abraxas, BACH1 and CtIP with the BRCT domain of BRCA1 are mutually exclusive, suggesting that the three proteins compete for the same binding site to form distinct BRCA1 containing complexes, of which only the Abraxas, BRCC36, BRCA1, and BARD1 complex is recruited to sites of DNA damage by RAP80 [XREF_BIBR]."
MiR-582-5p affects BRCC3
|
2
MiR-582-5p increases the amount of BRCC3.
|
1
reach
"These results meant that the inhibited effects of si-UCA1 on tumor progression were partly attenuated after cotransfection of si-UCA1 and miR-582-5p inhibitors.3.7.2
Simultaneously inhibited the expression of UCA1 and enhanced the expression of BRCC3 in pancreatic cancer cells, and then observed cell proliferation, apoptosis, and metastasis."
MiR-582-5p decreases the amount of BRCC3.
|
1
reach
"These results meant that the inhibited effects of si-UCA1 on tumor progression were partly attenuated after cotransfection of si-UCA1 and miR-582-5p inhibitors.3.7.2
Simultaneously inhibited the expression of UCA1 and enhanced the expression of BRCC3 in pancreatic cancer cells, and then observed cell proliferation, apoptosis, and metastasis."
Dibutyl phthalate affects BRCC3
2
|
Aflatoxin B1 affects BRCC3
2
|
Aflatoxin B1 increases the amount of BRCC3.
1
|
Aflatoxin B1 demethylates BRCC3.
1
|
UCA1 affects BRCC3
|
2
Plant Extracts affects BRCC3
2
|
Plant Extracts increases the amount of BRCC3.
1
|
Plant Extracts decreases the amount of BRCC3.
1
|
BRCC3 is modified
1
|
1
K63 affects BRCC3
|
2
BRISC deubiquitase affects BRCC3
|
2
reach
"Although Sagnier et al. [XREF_BIBR] suggested that autophagy selectively degrades HIV-1 Tat through a ubiquitin independent interaction with SQSTM1, Xu et al. demonstrated that HIV-1 Tat undergoes K63 polyubiquitination, a mark recognised by SQSTM1 and the NBR1 autophagy cargo receptor [XREF_BIBR, XREF_BIBR, XREF_BIBR], complexes with the CMA specific chaperone HSPA8 and is subjected to K63Ub selective autophagy mediated by serine hydroxymethyltransferase (SHMT) 1, SHMT2 and the BRCC36 and BRISC deubiquitase complex [XREF_BIBR]."
| PMC
BRCC3 affects α-SMA protein
|
2
BRCC3 affects lipopolysaccharide
|
2
BRCC3 affects cell death
|
2
BRCC3 inhibits cell death.
|
1
BRCC3 inhibits cell death. 1 / 1
|
1
BRCC3 activates cell death.
|
1
BRCC3 activates cell death. 1 / 1
|
1
BRCC3 affects calcium(2+)
|
2
BRCC3 inhibits calcium(2+). 2 / 2
|
2
reach
"Subsequently, through a series of comprehensive gain and loss-of-function experiments, we have reaffirmed the positive correlation between BRCC3 protein expression and USP15, confirming the pivotal role of USP15 in modulating the multiplication, invasiveness, and migration of bladder cancer by regulating BRCC3 expression.Subsequently, to assess the interaction between USP15 and BRCC3, we conducted meticulous Co-IP experiments, conclusively demonstrating direct binding between the two proteins."
reach
"Priming requires IRAK1 activation and proteasome dependent ERK activation (with downstream MEK1/2 activation), and it involves post-translational modifications including : (i) BRCC3 mediated NLRP3 deubiquitination, (ii) LUBAC mediated ASC ubiquitination, and (iii) SYK- and JNK dependent ASC phosphorylation."
reach
"Priming requires IRAK1 activation and proteasome dependent ERK activation (with downstream MEK1/2 activation), and it involves post-translational modifications including : (i) BRCC3 mediated NLRP3 deubiquitination, (ii) LUBAC mediated ASC ubiquitination, and (iii) SYK- and JNK dependent ASC phosphorylation."
BRCC3 affects Reperfusion Injury
|
2
BRCC3 activates Reperfusion Injury. 2 / 2
|
2
|
2
BRCC3 inhibits NLRP3 inflammasome complex assembly.
|
1
BRCC3 inhibits NLRP3 inflammasome complex assembly. 1 / 1
|
1
BRCC3 activates NLRP3 inflammasome complex assembly.
|
1
BRCC3 bound to NLRP3 activates NLRP3 inflammasome complex assembly. 1 / 1
|
1
BRCC3 affects K63
|
2
reach
"50
BRCC36 overexpression upregulates GSDMD expression and induces chronic pyroptosis, both of which deteriorate the tumor microenvironment (TME) over time and accelerate tumor growth, but this needs to be further studied.Furthermore, THL could inhibit the activity of the BRCC36 enzyme, reduce HMGCR protein levels, and suppress tumor growth."
BRCC3 affects Deubiquitinase
|
2
BRCC3 affects BRISC deubiquitase
|
2
reach
"Although Sagnier et al. [XREF_BIBR] suggested that autophagy selectively degrades HIV-1 Tat through a ubiquitin independent interaction with SQSTM1, Xu et al. demonstrated that HIV-1 Tat undergoes K63 polyubiquitination, a mark recognised by SQSTM1 and the NBR1 autophagy cargo receptor [XREF_BIBR, XREF_BIBR, XREF_BIBR], complexes with the CMA specific chaperone HSPA8 and is subjected to K63Ub selective autophagy mediated by serine hydroxymethyltransferase (SHMT) 1, SHMT2 and the BRCC36 and BRISC deubiquitase complex [XREF_BIBR]."
| PMC
ANRIL affects BRCC3
|
2
reach
"Receptor associated protein 80 (RAP80 or UIMC1) is an ubiquitin interaction motif containing (UIMC) nuclear protein that facilitates the recruitment of the BRCA1, BARD1, Abraxas, CCDC98, MERIT, and BRCC36 complex to DNA damage sites, which initiates DDR.6, 7, 8, 9, 10, 11, 12, 13 Although previous studies indicate that defective RAP80 function and expression could lead to genomic instability and subsequent increased early stage cancer risk,14, 15, 16 the possible role of RAP80 on tumor progression and malignancy in later stages, including EMT derived metastasis, has not been investigated."
2
|
2,3,7,8-tetrachlorodibenzodioxine increases the amount of BRCC3.
1
|
2,3,7,8-tetrachlorodibenzodioxine decreases the amount of BRCC3.
1
|
1
|
Torcetrapib affects BRCC3
1
|
Sodium arsenite affects BRCC3
1
|
Resveratrol affects BRCC3
1
|
Promethazine affects BRCC3
1
|
Potassium chromate affects BRCC3
1
|
Polyubiquitin foci affects BRCC3
|
1
Polyphenol affects BRCC3
1
|
Pentachlorophenol affects BRCC3
1
|
Paracetamol affects BRCC3
1
|
Ochratoxin A affects BRCC3
1
|
Nickel sulfate affects BRCC3
1
|
Nickel monoxide affects BRCC3
1
|
Mono(2-ethylhexyl) phthalate affects BRCC3
1
|
MiR-204 affects BRCC3
|
1
MiR-126-5p affects BRCC3
|
1
Methylmercury chloride affects BRCC3
1
|
Ivermectin affects BRCC3
1
|
Hsa-mir-4692 affects BRCC3
1
|
Hsa-mir-4635 affects BRCC3
1
|
Hsa-mir-4514 affects BRCC3
1
|
Hsa-mir-4269 affects BRCC3
1
|
Hsa-miR-92a-3p affects BRCC3
1
|
Hsa-miR-7977 affects BRCC3
1
|
Hsa-miR-7162-5p affects BRCC3
1
|
Hsa-miR-6715b-5p affects BRCC3
1
|
Hsa-miR-670-3p affects BRCC3
1
|
Hsa-miR-4743-3p affects BRCC3
1
|
Hsa-miR-3184-3p affects BRCC3
1
|
Hsa-miR-3157-5p affects BRCC3
1
|
Hsa-miR-208b-5p affects BRCC3
1
|
Hsa-miR-208a-5p affects BRCC3
1
|
Hsa-miR-193b-3p affects BRCC3
1
|
Homologous recombination affects BRCC3
|
1
Homologous recombination inhibits BRCC3. 1 / 1
|
1
Formaldehyde affects BRCC3
1
|
Folic acid affects BRCC3
1
|
Endosulfan affects BRCC3
1
|
Cyclohexyl isocyanate affects BRCC3
|
1
Cyclohexyl isocyanate activates BRCC3. 1 / 1
|
1
Copper(II) sulfate affects BRCC3
1
|
Cannabidiol affects BRCC3
1
|
Vascular Diseases affects BRCC3
|
1
Vascular Diseases inhibits BRCC3. 1 / 1
|
1
reach
"For the treatment of vascular diseases, silencing of ncRNAs provides potential therapeutic strategies by inducing ubiquitination degradation (miR-29a, miR-181b, lncRNA-Fendrr, lncRNA MIAT, lncRNA SNHG, miR-21, miR-424(322)) or inhibiting the deubiquitinating enzyme BRCC3/SUMO1 (lncRNA NEAT1, lncRNA SOX2-OT) (73, 82, 93, 96, 98, 100, 110, 111, 116)."
VD3 affects BRCC3
|
1
UIMC1 affects 63
|
1
UIM domains affects BRCC3
|
1
TEI affects BRCC3
|
1
TEAS affects BRCC3
|
1
SKL2001 affects BRCC3
|
1
Phosphatase affects BRCC3
|
1
Phosphatase dephosphorylates BRCC3. 1 / 1
|
1
Particulate Matter affects BRCC3
1
|
NLRP3 affects K63
|
1
N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal decreases the amount of BRCC3. 1 / 1
|
1
LncRNA ANRIL affects BRCC3
|
1
LDN 193189 affects BRCC3
1
|
K63-Ub 2 affects BRCC3
|
1
K63 affects NLRP3
|
1
K63 affects FLT3
|
1
JOSD2 affects BRCC3
|
1
Infections affects BRCC3
|
1
Infections decreases the amount of BRCC3. 1 / 1
|
1
Gentamicins affects BRCC3
1
|
FLT3 affects K63
|
1
Deletion BRCC3 affects BRCC3
|
1
DDSB site affects BRCC3
|
1
C60 fullerene affects BRCC3
1
|
BRCC3 affects ubiquitin-proteasome
|
1
BRCC3 affects regulation of cell cycle
|
1
BRCC3 activates regulation of cell cycle. 1 / 1
|
1
BRCC3 affects mineralization
|
1
BRCC3 inhibits mineralization. 1 / 1
|
1
BRCC3 affects mature IL-1beta
|
1
BRCC3 affects intestinal mucosal injury caused BMP2 ischemia-reperfusion PPARgamma signaling
|
1
BRCC3 affects interleukin-1 beta production
|
1
BRCC3 activates interleukin-1 beta production. 1 / 1
|
1
BRCC3 affects innate immune response
|
1
BRCC3 activates innate immune response. 1 / 1
|
1
BRCC3 affects deubiquitination such modification
|
1
BRCC3 affects deubiquitination sensitivity NLRP3
|
1
BRCC3 affects cytokine production
|
1
BRCC3 inhibits cytokine production. 1 / 1
|
1
BRCC3 affects cyclinB1
|
1
BRCC3 affects catenin
|
1
BRCC3 affects caspase-1 cleavage
|
1
BRCC3 affects carmustine
|
1
BRCC3 inhibits carmustine. 1 / 1
|
1
BRCC3 affects beta-catenin CRC cells
|
1
BRCC3 affects alkaline phosphatase
|
1
BRCC3 inhibits alkaline phosphatase. 1 / 1
|
1
BRCC3 affects activation BRCA1
|
1
BRCC3 affects UIM domains
|
1
BRCC3 affects TYROSINE-KINASE
|
1
BRCC3 inhibits TYROSINE-KINASE. 1 / 1
|
1
reach
"Priming requires IRAK1 activation and proteasome dependent ERK activation (with downstream MEK1/2 activation), and it involves post-translational modifications including : (i) BRCC3 mediated NLRP3 deubiquitination, (ii) LUBAC mediated ASC ubiquitination, and (iii) SYK- and JNK dependent ASC phosphorylation."
reach
"BRCC3 interference in HeLa and SiHa cells was revealed to suppress cell viability, invasion and migration abilities via upregulation of E-cadherin expression levels and downregulation of Vimentin, matrix metalloproteinase (MMP)-2, MMP-9, snail family transcriptional repressor (Snai) 1 and Snai2 expression levels."
|
1
BRCC3 ubiquitinates Putative leucine-rich repeat protein PS14. 1 / 1
|
1
BRCC3 affects PASMC
|
1
BRCC3 affects Nasopharyngeal Carcinoma
|
1
BRCC3 inhibits Nasopharyngeal Carcinoma. 1 / 1
|
1
BRCC3 affects NLRP3 receptor
|
1
BRCC3 affects NLRP3 inflammasome
|
1
BRCC3 affects NF-κB.
|
1
BRCC3 affects K63Ub
|
1
BRCC3 affects K63Ub deubiquitinase
|
1
reach
"In this way, BRCA1-A (i) accumulates BRCA1 at DSBs via RAP80-mediated recognition of Lys63-linked ubiquitin (K63Ub) adducts in the damaged chromatin [9, 15, 18], (ii) terminates the DDR via BRCC36-mediated K63Ub deubiquitinase (DUB)-activity [19] and (iii) prevents over-resection through sequestration of BRCA1 to the flanks of the DSBs, thereby depleting the local pool of BRCA1 available to enhance DNA end-resection by BRCA1-C [20]."
BRCC3 affects K63-Ub 2
|
1
BRCC3 affects K48Ub
|
1
BRCC3 affects JOSD2
|
1
BRCC3 affects Histone_H2A
1
|
BRCC3 affects Heart Failure
|
1
BRCC3 activates Heart Failure. 1 / 1
|
1
BRCC3 affects HBMVEC
|
1
BRCC3 affects Fig. 2E-H
|
1
BRCC3 affects FLAG-Tat protein
|
1
BRCC3 affects DSB-associated K63-Ub [
|
1
BRCC3 affects DNA_repair
1
|
BRCC3 affects DDSB site
|
1
reach
"At the endogenous level of TAZ (no doxycycline treatment), BRCC3 KD raised the expression of Cyr61, while upon TAZS89A expression, both TAZ target genes are significantly upregulated (Figure 2a), thus confirming the result of the screen.TAZ activity is mainly regulated by post-translational modifications, which affect its protein stability and its cellular localization [2,41]."
BRCC3 affects BRCC
|
1
BRCC3 affects BRCA1-BARD1
|
1
BRCC3 affects BRCA1-A
|
1
BRCC3 affects ATP-induced secretion mature IL-1beta
|
1
BRCC3 affects 63
|
1
AcLDL affects BRCC3
|
1
ABRAXAS1 affects UIM domains
|
1
63 affects UIMC1
|
1
2,4,6-tribromophenol affects BRCC3
1
|
1,2-dithiol-3-thione affects BRCC3
1
|
1,2-dimethylhydrazine affects BRCC3
1
|
(+)-catechin affects BRCC3
1
|
4,4'-sulfonyldiphenol affects BRCC3
1
|
1
|