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Molecular and Cellular Biology, April 1999, p. 2594-2600, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The c-fos Proto-Oncogene Is a Target for Transactivation by the p53 Tumor Suppressor

Adi Elkeles, Tamar Juven-Gershon, David Israeli, Sylvia Wilder, Amir Zalcenstein, and Moshe Oren*

Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

Received 26 October 1998/Returned for modification 21 December 1998/Accepted 6 January 1999

The p53 tumor suppressor gene is mutated in over 50% of human cancers, resulting in inactivation of the wild-type (wt) p53 protein. The most notable biochemical feature of p53 is its ability to act as a sequence-specific transcriptional activator. Through use of the suppression subtractive hybridization differential screening technique, we identified c-fos as a target for transcriptional stimulation by p53 in cells undergoing p53-mediated apoptosis. Overexpression of wt p53 induces c-fos mRNA and protein. Moreover, in vivo induction of c-fos in the thymus following whole-body exposure to ionizing radiation is p53 dependent. p53 responsiveness does not reside in the basal c-fos promoter. Rather, a distinct region within the c-fos gene first intron binds specifically to p53 and confers upon the c-fos promoter the ability to become transcriptionally activated by wt p53. Identification of c-fos as a specific target for transcriptional activation by p53 establishes a direct link between these two pivotal regulatory proteins and raises the possibility that c-fos contributes to some of the biological effects of p53.

* Corresponding author. Mailing address: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel. Phone: (972) 8-9342358. Fax: (972) 8-9465223. E-mail: lioren{at}dapsas1.weizmann.ac.il.

Molecular and Cellular Biology, April 1999, p. 2594-2600, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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