Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1

被引：195

作者：

Zheng, L ^{[1
]}

Pan, HY ^{[1
]}

Li, S ^{[1
]}

Flesken-Nikitin, A ^{[1
]}

Chen, PL ^{[1
]}

Boyer, TG ^{[1
]}

Lee, WH ^{[1
]}

机构：

[1] Univ Texas, Hlth Sci Ctr, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78229 USA

来源：

MOLECULAR CELL | 2000年 / 6卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1097-2765(00)00075-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BRCA1 has been implicated in the transcriptional regulation of DNA damage-inducible genes that function in cell cycle arrest. To explore the mechanistic basis for this regulation, a novel human gene, ZBRK1, which encodes a 60 kDa protein with an N-terminal KRAB domain and eight central zinc fingers, was identified by virtue of its interaction with BRCA1 in vitro and in vivo. ZBRK1 binds to a specific sequence, GGGxxx CAGxxxTTT, within GADD45 intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner. These results thus reveal a novel corepressor function for BRCA1 and provide a mechanistic basis for the biological activity of BRCA1 through sequence-specific transcriptional regulation.

引用

页码：757 / 768

页数：12

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