BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1

Elizabeth A. Williamson, Farnaz Dadmanesh, H. Phillip Koeffler

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

The p27Kip1 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 p27Kip1 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 p27Kip1. 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 p27Kip1 promoter. These results suggest that the transcriptional regulation of p27Kip1 by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.

Original languageEnglish (US)
Pages (from-to)3199-3206
Number of pages8
JournalOncogene
Volume21
Issue number20
DOIs
StatePublished - May 9 2002

Keywords

  • BRCA1
  • P27
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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