BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1

被引：49
|
作者：
Williamson, EA
Dadmanesh, F
Koeffler, HP
机构：
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Anat Pathol, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
来源：
ONCOGENE | 2002年 / 21卷 / 20期
关键词：
BRCA1; p27(Kip1); transcriptional regulation;
D O I：
10.1038/sj.onc.1205461
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：
The p27(Kip1) is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of P27(Kip1) and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27(Kip1). This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27(Kip1) promoter. These results suggest that the transcriptional regulation of p27(Kip1) by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.
引用
收藏
页码：3199 / 3206
页数：8
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