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BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1

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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.

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Acknowledgements

We thank B Weber, J Holt, J Wyke and T Sakai for the BRCA1 and p27Kip1 promoter constructs. EA Williamson is a recipient of a Postdoctoral Fellowship from the California Breast Cancer Research Program. HP Koeffler holds the endowed Mark Goodsen Chair of Oncology and is a member of the Jonsson Cancer Center. This work was supported by the Ko-So Foundation and the Parker Hughes Trust. We are grateful for the generous support of Norma Thorworth's Fund.

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Authors and Affiliations

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

    Elizabeth A Williamson & H Phillip Koeffler

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

    Farnaz Dadmanesh

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  1. Elizabeth A Williamson
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  2. Farnaz Dadmanesh
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Correspondence to Elizabeth A Williamson.

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Williamson, E., Dadmanesh, F. & Koeffler, H. BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1. Oncogene 21, 3199–3206 (2002). https://doi.org/10.1038/sj.onc.1205461

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