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Molecular and Cellular Biology, July 1999, p. 4843-4854, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

BRCA1 Is Phosphorylated at Serine 1497 In Vivo at a Cyclin-Dependent Kinase 2 Phosphorylation Site

Heinz Ruffner, Wei Jiang, A. Grey Craig, Tony Hunter, and Inder M. Verma*

The Salk Institute, La Jolla, California 92037

Received 6 January 1999/Returned for modification 25 February 1999/Accepted 26 March 1999

BRCA1 is a cell cycle-regulated nuclear protein that is phosphorylated mainly on serine and to a lesser extent on threonine residues. Changes in phosphorylation occur in response to cell cycle progression and DNA damage. Specifically, BRCA1 undergoes hyperphosphorylation during late G1 and S phases of the cell cycle. Here we report that BRCA1 is phosphorylated in vivo at serine 1497 (S1497), which is part of a cyclin-dependent kinase (CDK) consensus site. S1497 can be phosphorylated in vitro by CDK2-cyclin A or E. BRCA1 coimmunoprecipitates with an endogenous serine-threonine protein kinase activity that phosphorylates S1497 in vitro. This cellular kinase activity is sensitive to transfection of a dominant negative form of CDK2 as well as the application of the CDK inhibitors p21 and butyrolactone I but not p16. Furthermore, BRCA1 coimmunoprecipitates with CDK2 and cyclin A. These results suggest that the endogenous kinase activity is composed of CDK2-cyclin complexes, at least in part, concordant with the G1/S-specific increase in BRCA1 phosphorylation.

* Corresponding author. Mailing address: Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 453-4100, ext. 1462. Fax: (619) 558-7454. E-mail: verma{at}salk.edu.

Molecular and Cellular Biology, July 1999, p. 4843-4854, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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