BRCC3

Summary

Gene Symbol: BRCC3
Description: BRCA1/BRCA2-containing complex subunit 3
Alias: BRCC36, C6.1A, CXorf53, lys-63-specific deubiquitinase BRCC36, BRCA1-A complex subunit BRCC36, BRCA1/BRCA2-containing complex subunit 36, BRISC complex subunit BRCC36
Species: human
Products:     BRCC3

Top Publications

  1. Boudreau H, Broustas C, Gokhale P, Kumar D, Mewani R, Rone J, et al. Expression of BRCC3, a novel cell cycle regulated molecule, is associated with increased phospho-ERK and cell proliferation. Int J Mol Med. 2007;19:29-39 pubmed
    ..We report the initial characterization of BRCC3, a novel gene discovered previously by mRNA expression profiling in MDA-MB 231 human breast cancer cells treated ..
  2. Patterson Fortin J, Shao G, Bretscher H, Messick T, Greenberg R. Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex. J Biol Chem. 2010;285:30971-81 pubmed publisher
    b>BRCC36 is a JAMM (JAB1/MPN/Mov34 metalloenzyme) domain, lysine 63-ubiquitin (K63-Ub)-specific deubiquitinating enzyme (DUB) and a member of two protein complexes: the DNA damage-responsive BRCA1-RAP80 complex, and the cytoplasmic BRCC36 ..
  3. Wang B, Hurov K, Hofmann K, Elledge S. NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. Genes Dev. 2009;23:729-39 pubmed publisher
    ..analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE...
  4. Feng L, Wang J, Chen J. The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J Biol Chem. 2010;285:30982-8 pubmed publisher
    b>BRCC36 is a member of the JAMM/MPN(+) family of zinc metalloproteases that specifically cleaves Lys 63-linked polyubiquitin chains in vitro...
  5. Wang B, Elledge S. Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc Natl Acad Sci U S A. 2007;104:20759-63 pubmed
    The Brca1 A complex contains Brca1/Bard1, Abraxas, Rap80, and Brcc36; however, with the exception of the Brca1-Abraxas interaction, how the A complex is assembled is not known...
  6. Shao G, Lilli D, Patterson Fortin J, Coleman K, Morrissey D, Greenberg R. The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc Natl Acad Sci U S A. 2009;106:3166-71 pubmed publisher
    ..Inhibition of the Rap80-BRCC36 de-ubiquitinating enzyme complex partially restored DSB-associated ubiquitin levels following RNF8 knockdown or ..
  7. Feng L, Huang J, Chen J. MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev. 2009;23:719-28 pubmed publisher
    ..motif (UIM)-containing protein RAP80, a coiled-coil domain protein CCDC98/Abraxas, and a deubiquitinating enzyme BRCC36. Here we describe the characterization of a novel component of this complex, MERIT40 (Mediator of Rap80 ..
  8. Cooper E, Cutcliffe C, Kristiansen T, Pandey A, Pickart C, Cohen R. K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1. EMBO J. 2009;28:621-31 pubmed publisher
    ..proteasome, the COP9 signalosome (CSN) and a novel complex that includes the JAMM/MPN+ domain-containing protein Brcc36. When we analysed the individual complexes, we found that the activity was intrinsic to PA700 and the Brcc36 ..
  9. Dong Y, Hakimi M, Chen X, Kumaraswamy E, Cooch N, Godwin A, et al. Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol Cell. 2003;12:1087-99 pubmed
    ..BRCC not only displays increased association with p53 following DNA damage but also ubiquitinates p53 in vitro. BRCC36 and BRCC45 are novel components of the complex with sequence homology to a subunit of the signalosome and ..

More Information

Publications49

  1. Ambroggio X, Rees D, Deshaies R. JAMM: a metalloprotease-like zinc site in the proteasome and signalosome. PLoS Biol. 2004;2:E2 pubmed publisher
    ..The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors...
  2. Sobhian B, Shao G, Lilli D, Culhane A, Moreau L, Xia B, et al. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science. 2007;316:1198-202 pubmed
    ..the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gammaH2AX-dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs...
  3. Zheng H, Gupta V, Patterson Fortin J, Bhattacharya S, Katlinski K, Wu J, et al. A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses. Cell Rep. 2013;5:180-93 pubmed publisher
    ..The deubiquitinating enzyme (DUB) BRCC36 segregates into distinct nuclear and cytoplasmic complexes that are specific for K63-Ub hydrolysis...
  4. Hu X, Kim J, Castillo A, Huang M, Liu J, Wang B. NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes. J Biol Chem. 2011;286:11734-45 pubmed publisher
    b>BRCC36-deubiquitinating enzyme (DUB) forms two different complexes through interactions with two different adaptor proteins Abraxas and ABRO1 in cells...
  5. Cooper E, Boeke J, Cohen R. Specificity of the BRISC deubiquitinating enzyme is not due to selective binding to Lys63-linked polyubiquitin. J Biol Chem. 2010;285:10344-52 pubmed publisher
    BRISC (Brcc36-containing isopeptidase complex) is a four-subunit deubiquitinating (DUB) enzyme that has a catalytic subunit, called Brcc36, that is a member of the JAMM/MPN(+) family of zinc metalloproteases...
  6. Ren G, Zhang X, Xiao Y, Zhang W, Wang Y, Ma W, et al. ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination. EMBO J. 2019;38: pubmed publisher
    ..Furthermore, deficiency of BRCC3, the catalytically active component of BRISC, displays similar phenotypes to ABRO1 knockout mice...
  7. Liu Q, Wu Y, Qin Y, Hu J, Xie W, Qin F, et al. Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses. Sci Adv. 2018;4:eaar2824 pubmed publisher
    ..previously unrecognized roles of a subset of DUBs, including USP5, USP14, USP22, USP48, USP52, COPS5, and BRCC3, in inhibiting antiviral immunity at various levels...
  8. Xu M, Moresco J, Chang M, Mukim A, Smith D, Diedrich J, et al. SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy. PLoS Pathog. 2018;14:e1007071 pubmed publisher
    ..targets Serine Hydroxymethyltransferase 2 (SHMT2), a regulator of glycine biosynthesis and an adaptor for the BRCC36 K63Ub-specific deubiquitinase in the BRISC complex...
  9. Hu J, Wu H, Wang D, Yang Z, Dong J. LncRNA ANRIL promotes NLRP3 inflammasome activation in uric acid nephropathy through miR-122-5p/BRCC3 axis. Biochimie. 2019;157:102-110 pubmed publisher
    ..The expressions of ANRIL, miR-122-5p, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and NOD-like receptor protein 3 (NLRP3) were determined in UAN patients and uric acid-treated HK-2 cells by qRT-..
  10. Janczar S, Kosińska J, Ploski R, Pastorczak A, Wegner O, Zalewska Szewczyk B, et al. Haemophilia A and cardiovascular morbidity in a female SHAM syndrome carrier due to skewed X chromosome inactivation. Eur J Med Genet. 2016;59:43-7 pubmed publisher
    ..described a severe haemophilia A and moyamoya (SHAM) syndrome caused by Xq28 deletions encompassing F8 and the BRCC3 familial moyamoya gene. The phenotype includes haemophilia A, moyamoya angiopathy, dysmorphia and hypertension...
  11. Her J, Soo Lee N, Kim Y, Kim H. Factors forming the BRCA1-A complex orchestrate BRCA1 recruitment to the sites of DNA damage. Acta Biochim Biophys Sin (Shanghai). 2016;48:658-64 pubmed publisher
    ..Factors comprising the BRCA1-A include RAP80, CCDC98/Abraxas, BRCC36, BRCC45, BARD1, BRCA1, and MERIT40, a RAP80-associated factor...
  12. Lee B, Singh A, Mark Glover J, Hendzel M, Spyracopoulos L. Molecular Basis for K63-Linked Ubiquitination Processes in Double-Strand DNA Break Repair: A Focus on Kinetics and Dynamics. J Mol Biol. 2017;429:3409-3429 pubmed publisher
    ..E3 ligases RNF8 and RNF168, which is balanced through the binding and cleavage of chains by the deubiquitinase BRCC36, and the proteasome, and through the binding of chains by recognition modules on repair proteins such as RAP80...
  13. Gill H, Leung A, Kwong Y. Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy. Int J Mol Sci. 2016;17:440 pubmed publisher
    ..receptor signaling (JAK2, MPL, FLT3, GNAS, KIT), RAS pathways (KRAS, NRAS, CBL, NF1, PTPN11), DNA repair (ATM, BRCC3, DLRE1C, FANCL), and cohesion complexes (STAG2, CTCF, SMC1A, RAD21)...
  14. Ling H, Li S, Wu Y, Zheng Y, Qiao F, Yao L, et al. Genetic evaluation of BRCA1 associated a complex genes with triple-negative breast cancer susceptibility in Chinese women. Oncotarget. 2016;7:9759-72 pubmed publisher
    ..We detected 37 common variants in ABRAXAS, RAP80, BRE, BRCC36 and NBA1/MERIT40 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC...
  15. Wu J, Huen M, Lu L, Ye L, Dou Y, Ljungman M, et al. Histone ubiquitination associates with BRCA1-dependent DNA damage response. Mol Cell Biol. 2009;29:849-60 pubmed publisher
    ..Taken together, our results suggest that ubiquitinated histones H2A and H2B may recruit the BRCA1 complex to DNA damage lesions on the chromatin. ..
  16. Chi W, Hua X, Chen X, Bian F, Yuan X, Zhang L, et al. Mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye. J Autoimmun. 2017;80:65-76 pubmed publisher
    ..mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress...
  17. Tu Z, Xu B, Qu C, Tao Y, Chen C, Hua W, et al. BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro. Radiat Oncol. 2015;10:123 pubmed publisher
    b>BRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear...
  18. Ganguly B, Kadam N. Mutations of myelodysplastic syndromes (MDS): An update. Mutat Res Rev Mutat Res. 2016;769:47-62 pubmed publisher
    ..JAK2); RAS pathway (KRAS, NRAS, CBL, NF1, PTPN11); cohesin complex (STAG2, CTCF, SMC1A, RAD21); DNA repair (ATM, BRCC3, DLRE1C, FANCL); and other pathway genes have given insights into the independent effects and interaction of co-..
  19. Yan K, Li L, Wang X, Hong R, Zhang Y, Yang H, et al. The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells. J Cell Biol. 2015;210:209-24 pubmed publisher
    ..The BRCC36 isopeptidase complex (BRISC) is a DUB that is specific for lysine 63-linked ubiquitin hydrolysis; however, its ..
  20. Zhang J, Cao M, Dong J, Li C, Xu W, Zhan Y, et al. ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53. Nat Commun. 2014;5:5059 pubmed publisher
    ..Our study shows that ABRO1 is a novel p53 regulator that plays an important role in tumour suppression and the DNA damage response. ..
  21. Nikkilä J, Coleman K, Morrissey D, Pylkäs K, Erkko H, Messick T, et al. Familial breast cancer screening reveals an alteration in the RAP80 UIM domain that impairs DNA damage response function. Oncogene. 2009;28:1843-52 pubmed publisher
    ..Although evidently quite rare, these results suggest that critical constitutional mutations in RAP80 abrogate DDR function and may be involved in genetic predisposition to cancer. ..
  22. Hu X, Paul A, Wang B. Rap80 protein recruitment to DNA double-strand breaks requires binding to both small ubiquitin-like modifier (SUMO) and ubiquitin conjugates. J Biol Chem. 2012;287:25510-9 pubmed publisher
    ..These findings propose a model in which SUMO and Ub modification is coordinated to recruit Rap80 and BRCA1 to DNA damage sites. ..
  23. Guzzo C, Berndsen C, Zhu J, Gupta V, Datta A, Greenberg R, et al. RNF4-dependent hybrid SUMO-ubiquitin chains are signals for RAP80 and thereby mediate the recruitment of BRCA1 to sites of DNA damage. Sci Signal. 2012;5:ra88 pubmed publisher
    ..Our findings, therefore, connect ubiquitin- and SUMO-dependent DSB recognition, revealing that RNF4-synthesized hybrid SUMO-ubiquitin chains are recognized by RAP80 to promote BRCA1 recruitment and DNA repair. ..
  24. Kumaraswamy E, Shiekhattar R. Activation of BRCA1/BRCA2-associated helicase BACH1 is required for timely progression through S phase. Mol Cell Biol. 2007;27:6733-41 pubmed
    ..These results point to a critical role for BACH1 helicase activity not only in the timely progression through the S phase but also in maintaining genomic stability. ..
  25. Zeqiraj E, Tian L, Piggott C, Pillon M, Duffy N, Ceccarelli D, et al. Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function. Mol Cell. 2015;59:970-83 pubmed publisher
    b>BRCC36 is a Zn(2+)-dependent deubiquitinating enzyme (DUB) that hydrolyzes lysine-63-linked ubiquitin chains as part of distinct macromolecular complexes that participate in either interferon signaling or DNA-damage recognition...
  26. Cho H, Oh Y, Han S, Chung H, Kim C, Lee N, et al. Cdk1 protein-mediated phosphorylation of receptor-associated protein 80 (RAP80) serine 677 modulates DNA damage-induced G2/M checkpoint and cell survival. J Biol Chem. 2013;288:3768-76 pubmed publisher
    ..These results suggest that post-translational phosphorylation of RAP80 by the Cdk1-cyclin B(1) complex is important for RAP80 functional sensitivity to IR and G(2)/M checkpoint control. ..
  27. Zhu B, Yan K, Li L, Lin M, Zhang S, He Q, et al. K63-linked ubiquitination of FANCG is required for its association with the Rap80-BRCA1 complex to modulate homologous recombination repair of DNA interstand crosslinks. Oncogene. 2015;34:2867-78 pubmed publisher
    ..In addition, we demonstrated that K63Ub-modified FANCG was deubiquitinated by BRCC36 complex in vitro and in vivo. Inhibition of BRCC36 resulted in increased K63Ub modification of FANCG...
  28. Kenwrick S, Levinson B, Taylor S, Shapiro A, Gitschier J. Isolation and sequence of two genes associated with a CpG island 5' of the factor VIII gene. Hum Mol Genet. 1992;1:179-86 pubmed
    ..1B define a region of Xq28 that is deleted in two brothers that suffer from mental handicap and dysmorphism as well as hemophilia A. Thus, this region is likely to contain loci that are important for physical and mental development. ..
  29. Solyom S, Aressy B, Pylkäs K, Patterson Fortin J, Hartikainen J, Kallioniemi A, et al. Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions. Sci Transl Med. 2012;4:122ra23 pubmed publisher
    ..1082G>A mutation connects to cancer predisposition. These findings contribute to the concept of a BRCA-centered tumor suppressor network and provide the identity of Abraxas as a new breast cancer susceptibility gene. ..
  30. Shao G, Patterson Fortin J, Messick T, Feng D, Shanbhag N, Wang Y, et al. MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks. Genes Dev. 2009;23:740-54 pubmed publisher
    Rap80 targets the breast cancer suppressor protein BRCA1 along with Abraxas and the BRCC36 deubiquitinating enzyme (DUB) to polyubiquitin structures at DNA double-strand breaks (DSBs)...
  31. Fisch P, Forster A, Sherrington P, Dyer M, Rabbitts T. The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another. Oncogene. 1993;8:3271-6 pubmed
    ..In any event, this is the first cloned gene which is implicated in pathogenesis of chronic/pro-lymphocytic leukaemia of the T-cell lineage. ..
  32. Sun Z, Zhang T, Ning K, Zhu R, Liu F, Tang S, et al. B7-H3 upregulates BRCC3 expression, antagonizing DNA damage caused by 5-Fu. Oncol Rep. 2016;36:231-8 pubmed publisher
    ..Our previous mRNA microarray data revealed that BRCC3, a component of the BRCA1-BRCA2-BRCC3 DNA repair complex, had a direct relationship with B7-H3, an immunoglobulin ..
  33. Kyrieleis O, McIntosh P, Webb S, Calder L, Lloyd J, Patel N, et al. Three-Dimensional Architecture of the Human BRCA1-A Histone Deubiquitinase Core Complex. Cell Rep. 2016;17:3099-3106 pubmed publisher
    ..The structure of an active core complex comprising two Abraxas/BRCC36/BRCC45/MERIT40 tetramers determined by negative-stain electron microscopy (EM) reveals a distorted V-shape ..
  34. Miskinyte S, Butler M, Herve D, Sarret C, Nicolino M, Petralia J, et al. Loss of BRCC3 deubiquitinating enzyme leads to abnormal angiogenesis and is associated with syndromic moyamoya. Am J Hum Genet. 2011;88:718-728 pubmed publisher
    ..We show that this syndromic moyamoya is caused by Xq28 deletions removing MTCP1/MTCP1NB and BRCC3. We also show that brcc3 morphant zebrafish display angiogenesis defects that are rescued by endothelium-specific ..
  35. Chai K, Wang C, Liaw H, Fang K, Yang C, Tzeng S. Downregulation of BRCA1-BRCA2-containing complex subunit 3 sensitizes glioma cells to temozolomide. Oncotarget. 2014;5:10901-15 pubmed
    We previously found that BRCA1-BRCA2-containing complex subunit 3 (BRCC3) was highly expressed in tumorigenic rat glioma cells. However, the functional role of BRCC3 in human glioma cells remains to be characterized...
  36. Coleman K, Greenberg R. The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection. J Biol Chem. 2011;286:13669-80 pubmed publisher
    ..RAP80 or BRCC36 deficiency resulted in elevated Mre11-CtIP-dependent 5' end resection with a concomitant increase in HDR ..
  37. Huang D, Nagata Y, Grossmann V, Radivoyevitch T, Okuno Y, Nagae G, et al. BRCC3 mutations in myeloid neoplasms. Haematologica. 2015;100:1051-7 pubmed publisher
    ..1444 cases analyzed by next generation sequencing, somatic mutations in the gene BRCA1-BRCA2-containing complex 3 (BRCC3) were identified in 28 cases (1.9%)...
  38. Hu Y, Petit S, Ficarro S, Toomire K, Xie A, Lim E, et al. PARP1-driven poly-ADP-ribosylation regulates BRCA1 function in homologous recombination-mediated DNA repair. Cancer Discov. 2014;4:1430-47 pubmed publisher
    ..Thus, hyperfunctioning BRCA1 can elicit genomic abnormalities similar to those observed in the absence of certain BRCA1 functions. ..
  39. Ng H, Wei L, Lan L, Huen M. The Lys63-deubiquitylating Enzyme BRCC36 Limits DNA Break Processing and Repair. J Biol Chem. 2016;291:16197-207 pubmed publisher
    ..to its function at DNA double strand breaks (DSBs), we used RNAi and genome editing approaches to target BRCC36, the protein subunit that confers the BRCA1-A complex its DUB activity...
  40. Tripathi E, Smith S. Cell cycle-regulated ubiquitination of tankyrase 1 by RNF8 and ABRO1/BRCC36 controls the timing of sister telomere resolution. EMBO J. 2017;36:503-519 pubmed publisher
    ..K63-linked ubiquitin chains to tankyrase 1, while in G1 phase such ubiquitin chains are removed by BRISC, an ABRO1/BRCC36-containing deubiquitinase complex...