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Molecular and Cellular Biology, October 2000, p. 7450-7459, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Tumor Suppressor p53 Is Required To Modulate BRCA1 Expression

Paz Arizti,1 Li Fang,2 Iha Park,1 Yuxin Yin,3 Ellen Solomon,4 Toru Ouchi,2 Stuart A. Aaronson,2 and Sam W. Lee1,*

Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 021151; The Derald H. Ruttenberg Cancer Center, The Mount Sinai Medical School, New York, New York 100292; Department of Molecular Biology, Princeton University, Princeton, New Jersey 085443; and Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London SE1 9RT, United Kingdom4

Received 14 June 2000/Returned for modification 17 July 2000/Accepted 21 July 2000

Individuals carrying mutations in BRCA1 or p53 genes are predisposed to a variety of cancers, and both tumor suppressor genes have been implicated in DNA damage response pathways. We have analyzed a possible functional link between p53 and BRCA1 genes. Here we show that BRCA1 expression levels are down-regulated in response to p53 induction in cells that undergo either growth arrest, senescence, or apoptosis. Physiological stimuli, such as exposure to DNA-damaging agents, also result in negative regulation of BRCA1 levels in a p53-dependent manner prior to causing cell cycle arrest. Nuclear run-on experiments and luciferase reporter assays demonstrate that the changes in BRCA1 expression are mainly due to transcriptional repression induced by p53. In conclusion, the data show that BRCA1 expression levels are controlled by the presence and activity of wild-type p53 and suggest the existence of an intracellular p53/BRCA1 pathway in the response of cells to stress conditions.

* Corresponding author. Mailing address: Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Suite 921, 77 Ave. Louis Pasteur, Boston, MA 02115. Phone: (617) 667-8563. Fax: (617) 667-0980. E-mail: slee2{at}caregroup.harvard.edu.

Molecular and Cellular Biology, October 2000, p. 7450-7459, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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