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Molecular and Cellular Biology, May 2002, p. 2928-2938, Vol. 22, No. 9
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.9.2928-2938.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

p53 Is Necessary for the Apoptotic Response Mediated by a Transient Increase of Ras Activity

Peihong Ma,¹ Maureen Magut,¹ XinBin Chen,² and Chang-Yan Chen^1*

Cancer Research Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts,¹ Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama²

Received 23 August 2001/ Returned for modification 22 October 2001/ Accepted 29 January 2002

The tumor suppressor p53 eliminates cancer-prone cells via multiple mechanisms, including apoptosis. Ras elicits apoptosis in cells after protein kinase C (PKC) downregulation. However, the role of p53 in Ras-mediated apoptosis has not been fully investigated. Here, we demonstrate that mouse fibroblasts that express wild-type p53 are more susceptible to apoptosis elicited by PKC inhibition if Ras is transiently expressed or upregulated as opposed to stably expressed. In the latter case, p53 is frequently mutated. Transiently increased Ras activity induces Bax, and PKC inhibition augments this induction. Overexpression of E6 inactivates p53 and thereby suppresses both Bax induction and apoptosis. In contrast, Bax is not induced in stable ras transfectants, regardless of PKC inhibition. The data suggest that short- and long-term activation of Ras use a different mechanism(s) to initiate apoptosis. The status of p53 may contribute to such differences.

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* Corresponding author. Mailing address: Cancer Research Center, Boston University School of Medicine, 80 East Concord St., R 908, Boston, MA 02118. Phone: (617) 638-4128. Fax: (617) 638-4176. E-mail: yanyan{at}bu.edu.

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Molecular and Cellular Biology, May 2002, p. 2928-2938, Vol. 22, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.9.2928-2938.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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