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BRCA1 transactivates the cyclin-dependent kinase inhibitor p27(Kip1)
Elizabeth A Williamson1, Farnaz Dadmanesh, H Phillip Koeffler
1Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA. williamsone@cshs.org
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.