Autoubiquitination of the BRCA1·BARD1 RING Ubiquitin Ligase*

The RING finger of BRCA1 confers ubiquitin ligase activity that is markedly enhanced when complexed with another RING-containing protein, BARD1, and is required for the function of this tumor suppressor protein in protecting genomic integrity. Here, we report that co-expression of BRCA1-(1–639) and BARD1 in bacteria can assemble a potent ubiquitin ligase activity. Purified BRCA1-(1–639)·BARD1 stimulated the Ubc5c-mediated monoubiquitination of histone H2A/H2AX in vitro, suggesting a possible role for BRCA1·BARD1 in modifying chromatin structure. Moreover, the truncated BRCA1·BARD1 complex exhibited efficient autoubiquitination activity in vitro capable of assembling non-lysine 48-linked polyubiquitin chains on both BRCA1-(1–639) and BARD1. When co-expressed in cells by transient transfection, the recombinant BRCA1-(1–300)·BARD1 complex was found to be associated with polyubiquitin chains, suggesting that BRCA1-(1–300)·BARD1 was ubiquitinated in vivo as well. These results raise the possibility that BRCA1·BARD1 acts to assemble non-lysine 48-linked polyubiquitin chains that may serve as part of a signaling platform required for coordinating DNA repair-related events.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-06-14

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M201252200PMID 11927591
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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