BARD1

BRCA1 associated RING domain 1

PDB rendering based on 1jm7.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolBARD1
External IDsOMIM: 601593 MGI: 1328361 HomoloGene: 400 ChEMBL: 1741211 GeneCards: BARD1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez58012021
EnsemblENSG00000138376ENSMUSG00000026196
UniProtQ99728O70445
RefSeq (mRNA)NM_000465NM_007525
RefSeq (protein)NP_000456NP_031551
Location (UCSC)Chr 2:
215.59 – 215.67 Mb		Chr 1:
71.03 – 71.1 Mb
PubMed search

BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.[1][2][3]

Function

BARD1 and BRCA1 form a heterodimer via their N-terminal RING finger domains. The BARD1-BRCA1 interaction is observed in vivo and in vitro and is essential for BRCA1 stability. BARD1 shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes, and developmentally important genes such as the polycomb group of genes. The BARD1 protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. BARD1 may be the target of oncogenic mutations in breast or ovarian cancer.[4] BARD1 expression is upregulated by genotoxic stress and involved in apoptosis through binding and stabilizing p53 independently of BRCA1.[5]

Interactions

BARD1 has been shown to interact with:

References

  1. ↑ 1.0 1.1 Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL, Yang MC, Hwang LY, Bowcock AM, Baer R (January 1997). "Identification of a RING protein that can interact in vivo with the BRCA1 gene product". Nat Genet 14 (4): 430–440. doi:10.1038/ng1296-430. PMID 8944023.
  2. ↑ Thai TH, Du F, Tsan JT, Jin Y, Phung A, Spillman MA, Massa HF, Muller CY, Ashfaq R, Mathis JM, Miller DS, Trask BJ, Baer R, Bowcock AM (March 1998). "Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers". Hum Mol Genet 7 (2): 195–202. doi:10.1093/hmg/7.2.195. PMID 9425226.
  3. ↑ 3.0 3.1 Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA, Khanna KK (July 2004). "BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage". J Biol Chem 279 (30): 31251–31258. doi:10.1074/jbc.M405372200. PMID 15159397.
  4. ↑ "Entrez Gene: BARD1 BRCA1 associated RING domain 1".
  5. ↑ Irminger-Finger I, Leung WC, Li J, Dubois-Dauphin M, Harb J, Feki A, Jefford CE, Soriano JV, Jaconi M, Montesano R, Krause KH (December 2001). "Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis". Mol. Cell 8 (6): 1255–66. doi:10.1016/s1097-2765(01)00406-3. PMID 11779501.
  6. ↑ 6.0 6.1 6.2 6.3 Ryser S, Dizin E, Jefford CE, Delaval B, Gagos S, Christodoulidou A, Krause KH, Birnbaum D, Irminger-Finger I (February 2009). "Distinct roles of BARD1 isoforms in mitosis: full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2". Cancer Res. 69 (3): 1125–34. doi:10.1158/0008-5472.CAN-08-2134. PMID 19176389.
  7. ↑ Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG, Scheidereit C, Leutz A (June 1999). "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators". Oncogene 18 (22): 3316–23. doi:10.1038/sj.onc.1202717. PMID 10362352.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R (November 2003). "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair". Mol. Cell 12 (5): 1087–99. doi:10.1016/S1097-2765(03)00424-6. PMID 14636569.
  9. ↑ 9.0 9.1 9.2 Mallery DL, Vandenberg CJ, Hiom K (Dec 2002). "Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains". EMBO J. 21 (24): 6755–62. doi:10.1093/emboj/cdf691. PMC 139111. PMID 12485996.
  10. ↑ 10.0 10.1 Kentsis A, Gordon RE, Borden KL (November 2002). "Control of biochemical reactions through supramolecular RING domain self-assembly". Proc. Natl. Acad. Sci. U.S.A. 99 (24): 15404–9. doi:10.1073/pnas.202608799. PMC 137729. PMID 12438698.
  11. ↑ 11.0 11.1 11.2 Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ (June 2002). "Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase". J. Biol. Chem. 277 (24): 22085–92. doi:10.1074/jbc.M201252200. PMID 11927591.
  12. ↑ 12.0 12.1 12.2 Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T (July 2004). "Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (30): 30919–22. doi:10.1074/jbc.C400169200. PMID 15184379.
  13. ↑ 13.0 13.1 Wu-Baer F, Lagrazon K, Yuan W, Baer R (September 2003). "The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin". J. Biol. Chem. 278 (37): 34743–6. doi:10.1074/jbc.C300249200. PMID 12890688.
  14. ↑ 14.0 14.1 14.2 Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ (July 2003). "BRCA1-independent ubiquitination of FANCD2". Mol. Cell 12 (1): 247–54. doi:10.1016/S1097-2765(03)00281-8. PMID 12887909.
  15. ↑ 15.0 15.1 Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T (May 2001). "The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation". J. Biol. Chem. 276 (18): 14537–40. doi:10.1074/jbc.C000881200. PMID 11278247.
  16. ↑ 16.0 16.1 16.2 Kleiman FE, Manley JL (March 2001). "The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression". Cell 104 (5): 743–53. doi:10.1016/S0092-8674(01)00270-7. PMID 11257228.
  17. ↑ 17.0 17.1 17.2 Kleiman FE, Manley JL (September 1999). "Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50". Science 285 (5433): 1576–9. doi:10.1126/science.285.5433.1576. PMID 10477523.
  18. ↑ Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene MI (August 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. PMID 11498787.
  19. ↑ Fabbro M, Rodriguez JA, Baer R, Henderson BR (June 2002). "BARD1 induces BRCA1 intranuclear foci formation by increasing RING-dependent BRCA1 nuclear import and inhibiting BRCA1 nuclear export". J. Biol. Chem. 277 (24): 21315–24. doi:10.1074/jbc.M200769200. PMID 11925436.
  20. ↑ Rodriguez JA, Schüchner S, Au WW, Fabbro M, Henderson BR (March 2004). "Nuclear-cytoplasmic shuttling of BARD1 contributes to its proapoptotic activity and is regulated by dimerization with BRCA1". Oncogene 23 (10): 1809–20. doi:10.1038/sj.onc.1207302. PMID 14647430.
  21. ↑ Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M, Ohta T, Klevit R (May 2003). "Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex". Proc. Natl. Acad. Sci. U.S.A. 100 (10): 5646–51. doi:10.1073/pnas.0836054100. PMC 156255. PMID 12732733.
  22. ↑ Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit RE, Fukuda M, Ohta T (February 2004). "Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (6): 3916–24. doi:10.1074/jbc.M308540200. PMID 14638690.
  23. ↑ Chiba N, Parvin JD (October 2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID 11504724.
  24. ↑ Morris JR, Keep NH, Solomon E (March 2002). "Identification of residues required for the interaction of BARD1 with BRCA1". J. Biol. Chem. 277 (11): 9382–6. doi:10.1074/jbc.M109249200. PMID 11773071.
  25. ↑ Brzovic PS, Meza JE, King MC, Klevit RE (November 2001). "BRCA1 RING domain cancer-predisposing mutations. Structural consequences and effects on protein-protein interactions". J. Biol. Chem. 276 (44): 41399–406. doi:10.1074/jbc.M106551200. PMID 11526114.
  26. ↑ Xia Y, Pao GM, Chen HW, Verma IM, Hunter T (February 2003). "Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein". J. Biol. Chem. 278 (7): 5255–63. doi:10.1074/jbc.M204591200. PMID 12431996.
  27. ↑ Meza JE, Brzovic PS, King MC, Klevit RE (February 1999). "Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1". J. Biol. Chem. 274 (9): 5659–65. doi:10.1074/jbc.274.9.5659. PMID 10026184.
  28. ↑ Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE (October 2001). "Structure of a BRCA1-BARD1 heterodimeric RING-RING complex". Nat. Struct. Biol. 8 (10): 833–7. doi:10.1038/nsb1001-833. PMID 11573085.
  29. ↑ Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (September 1998). "The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression". J. Biol. Chem. 273 (39): 25388–92. doi:10.1074/jbc.273.39.25388. PMID 9738006.
  30. ↑ Jin Y, Xu XL, Yang MC, Wei F, Ayi TC, Bowcock AM, Baer R (October 1997). "Cell cycle-dependent colocalization of BARD1 and BRCA1 proteins in discrete nuclear domains". Proc. Natl. Acad. Sci. U.S.A. 94 (22): 12075–80. doi:10.1073/pnas.94.22.12075. PMC 23707. PMID 9342365.
  31. ↑ Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, Livingston DM (Dec 1999). "Genetic analysis of BRCA1 function in a defined tumor cell line". Mol. Cell 4 (6): 1093–9. doi:10.1016/S1097-2765(00)80238-5. PMID 10635334.
  32. ↑ Tascou S, Kang TW, Trappe R, Engel W, Burfeind P (September 2003). "Identification and characterization of NIF3L1 BP1, a novel cytoplasmic interaction partner of the NIF3L1 protein". Biochem. Biophys. Res. Commun. 309 (2): 440–8. doi:10.1016/j.bbrc.2003.07.008. PMID 12951069.
  33. ↑ Benezra M, Chevallier N, Morrison DJ, MacLachlan TK, El-Deiry WS, Licht JD (July 2003). "BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit". J. Biol. Chem. 278 (29): 26333–41. doi:10.1074/jbc.M303076200. PMID 12700228.
  34. ↑ Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, Wahrer DC, Sgroi DC, Lane WS, Haber DA, Livingston DM (April 2001). "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function". Cell 105 (1): 149–60. doi:10.1016/S0092-8674(01)00304-X. PMID 11301010.
  35. ↑ Wang Q, Zhang H, Kajino K, Greene MI (October 1998). "BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells". Oncogene 17 (15): 1939–48. doi:10.1038/sj.onc.1202403. PMID 9788437.
  36. ↑ Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, Fukuda M, Ohta T (January 2009). "BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity". Cancer Res. 69 (1): 111–9. doi:10.1158/0008-5472.CAN-08-3355. PMID 19117993.
  37. ↑ Spahn L, Petermann R, Siligan C, Schmid JA, Aryee DN, Kovar H (August 2002). "Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway". Cancer Res. 62 (16): 4583–7. PMID 12183411.

Further reading

  • Irminger-Finger I, Leung WC (2002). "BRCA1-dependent and independent functions of BARD1". Int. J. Biochem. Cell Biol. 34 (6): 582–587. doi:10.1016/S1357-2725(01)00161-3. PMID 11943588.
  • Irminger-Finger I (2003). "3rd Geneva aging workshop 2002: cancer, apoptosis and aging". Biochim. Biophys. Acta 1653 (1): 41–5. doi:10.1016/S0304-419X(03)00019-2. PMID 12781370.
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
  • Jin Y; Xu XL; Yang MC et al. (1997). "Cell cycle-dependent colocalization of BARD1 and BRCA1 proteins in discrete nuclear domains". Proc. Natl. Acad. Sci. U.S.A. 94 (22): 12075–12080. doi:10.1073/pnas.94.22.12075. PMC 23707. PMID 9342365.
  • Suzuki Y; Yoshitomo-Nakagawa K; Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Yu X; Wu LC; Bowcock AM et al. (1998). "The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression". J. Biol. Chem. 273 (39): 25388–25392. doi:10.1074/jbc.273.39.25388. PMID 9738006.
  • Ayi TC; Tsan JT; Hwang LY et al. (1998). "Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein". Oncogene 17 (16): 2143–2148. doi:10.1038/sj.onc.1202123. PMID 9798686.
  • Meza JE, Brzovic PS, King MC, Klevit RE (1999). "Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1". J. Biol. Chem. 274 (9): 5659–5665. doi:10.1074/jbc.274.9.5659. PMID 10026184.
  • Dechend R; Hirano F; Lehmann K et al. (1999). "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators". Oncogene 18 (22): 3316–3323. doi:10.1038/sj.onc.1202717. PMID 10362352.
  • Kleiman FE, Manley JL (1999). "Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50". Science 285 (5433): 1576–1579. doi:10.1126/science.285.5433.1576. PMID 10477523.
  • Scully R; Ganesan S; Vlasakova K et al. (2000). "Genetic analysis of BRCA1 function in a defined tumor cell line". Mol. Cell 4 (6): 1093–1099. doi:10.1016/S1097-2765(00)80238-5. PMID 10635334.
  • Yu X, Baer R (2000). "Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor". J. Biol. Chem. 275 (24): 18541–18549. doi:10.1074/jbc.M909494199. PMID 10764811.
  • Kleiman FE, Manley JL (2001). "The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression". Cell 104 (5): 743–753. doi:10.1016/S0092-8674(01)00270-7. PMID 11257228.
  • Hashizume R; Fukuda M; Maeda I et al. (2001). "The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation". J. Biol. Chem. 276 (18): 14537–14540. doi:10.1074/jbc.C000881200. PMID 11278247.
  • Wang Q; Zhang H; Guerrette S et al. (2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene 20 (34): 4640–4649. doi:10.1038/sj.onc.1204625. PMID 11498787.
  • Chiba N, Parvin JD (2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–38554. doi:10.1074/jbc.M105227200. PMID 11504724.
  • Brzovic PS, Meza JE, King MC, Klevit RE (2001). "BRCA1 RING domain cancer-predisposing mutations. Structural consequences and effects on protein-protein interactions". J. Biol. Chem. 276 (44): 41399–41406. doi:10.1074/jbc.M106551200. PMID 11526114.