The C-terminal (BRCT) domains of BRCA1 interact in vive with CtIP, a protein implicated in the CtBP pathway of transcriptional repression

Xin Yu, Leeju C. Wu, Anne M. Bowcock, Ami Aronheim, Richard Baer

Research output: Contribution to journalArticlepeer-review

340 Scopus citations

Abstract

The BRCA1 tumor suppresser encodes a polypeptide with two recognizable protein motifs: a RING domain near the N terminus and two tandem BRCT domains at the C terminus. Studies of tumor-associated mutations indicate that the RING and BRCT sequences are required for BRCA1-mediated tumor suppression. In addition, recent work has shown that BRCA1 is a potent regulator of RNA transcription and that the BRCT domains are also essential for this activity. Therefore, we used the Sos recruitment system to screen for proteins that bind this critical region of BRCA1. Our results show that the BRCT domains interact in vivo with CtIP, a protein originally identified on the basis of its association with the CtBP transcriptional co-represser. This finding suggests that BRCA1 regulates gene expression, at least in part, by modulating CtBP-mediated transcriptional repression. Moreover, the in vivo interaction between BRCA1 and CtIP is completely ablated by each of three independent tumor-associated mutations affecting the BRCT motifs of BRCA1. These results indicate that the BRCA1-CtIP interaction may be required for tumor suppression by BRCA1.

Original languageEnglish
Pages (from-to)25388-25392
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number39
DOIs
StatePublished - 25 Sep 1998
Externally publishedYes

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