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Originally published In Press as doi:10.1074/jbc.M203793200 on October 25, 2002

J. Biol. Chem., Vol. 278, Issue 1, 462-470, January 3, 2003
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DNA Damage-induced Inhibition of Securin Expression Is Mediated by p53*

Yunli Zhou, Kshama R. MehtaDagger , Andrew P. Choi§, Staci Scolavino, and Xun Zhang

From the Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Tumor suppressor p53 induces the cellular response to DNA damage mainly by regulating expression of its downstream target genes. The human securin is an anaphase inhibitor, preventing premature chromosome separation through inhibition of separase activity. It is also known as the product of the human pituitary tumor-transforming gene, pttg, a proto-oncogene. Here we report that the expression of human securin is suppressed in cells treated with the DNA-damaging drugs doxorubicin and bleomycin. This suppression requires functional p53. Analysis of the human securin promoter reveals that DNA-binding sites for Sp1 and NF-Y are both required for activation of securin expression; however, only the NF-Y site is essential for the suppression by p53. Our study indicates that securin is a p53 target gene and may play a role in p53-mediated cellular response to DNA damage.

* This work was supported in part by National Institutes of Health Individual National Research Service Award 5 F32 CA88519-02 (to Y. Z.) and Grant IRG-87-007-13 from the American Cancer Society.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Present address: Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143.

§ Present address: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

To whom correspondence should be addressed: Massachusetts General Hospital, Neuroendocrine Unit, 55 Fruit St., Bulfinch 457, Boston, MA 02114. Tel.: 617-724-7392; Fax: 617-726-5072; E-mail: xzhang5@partners.org.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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