乳腺癌1号基因（BRCA1）可反式激活细胞周期蛋白依赖性激酶抑制剂p27（Kip1）。

BRCA1 transactivates the cyclin-dependent kinase inhibitor p27(Kip1).

作者信息

Williamson Elizabeth A, Dadmanesh Farnaz, Koeffler H Phillip

机构信息

Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.

出版信息

Oncogene. 2002 May 9;21(20):3199-206. doi: 10.1038/sj.onc.1205461.

DOI:10.1038/sj.onc.1205461

PMID:12082635

Abstract

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.

摘要

p27（Kip1）是通用细胞周期蛋白依赖性激酶抑制剂家族的成员。先前，对一系列乳腺癌细胞系的免疫化学分析表明p27（Kip1）的表达与乳腺癌易感基因BRCA1之间存在相关性。BRCA1具有多种活性，包括DNA修复、生长抑制以及作为转录因子。在此我们证明BRCA1可反式激活p27（Kip1）的表达。这种反式激活依赖于功能性C末端反式激活结构域的存在。启动子缺失分析确定在p27（Kip1）启动子的-615至-511位存在一个假定的BRCA1反应元件。这些结果表明BRCA1对p27（Kip1）的转录调控可能是BRCA1诱导生长抑制的一种机制。