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Volume 272, Number 24, Issue of June 13, 1997 pp. 15049-15052
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
Identification of the MDM2 Oncoprotein as a Substrate for CPP32-like Apoptotic Proteases

(Received for publication, March 14, 1997, and in revised form, April 9, 1997)

Peter Erhardt , Kevin J. Tomaselli ^§ and Geoffrey M. Cooper

From the  Division of Molecular Genetics, Dana-Farber Cancer Institute and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 and ^§ IDUN Pharmaceuticals, Inc., La Jolla, California 92037

Programmed cell death is mediated by members of the interleukin 1- convertase family of proteases, which are activated in response to diverse cell death stimuli. However, the key substrates of these proteases that are responsible for apoptotic cell death have not been identified. Here we report that the MDM2 oncoprotein is cleaved by members of the CPP32 subfamily of interleukin 1- convertase proteases both in vitro and in vivo, resulting in the disappearance of MDM2 from apoptotic cells. Because MDM2 functions as a negative regulator of the p53 tumor suppressor and because p53 induces apoptosis in response to a variety of stimuli, this cleavage of MDM2 by CPP32-like proteases may result in deregulation of p53 and contribute directly to the process of apoptotic cell death.

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