BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1

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.