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Institute for Molecular Virology, Saint Louis University Health Sciences Center, St. Louis, Missouri 63110 [E. J. U., C. D-E., T. S., G. C.], and The Ben May Institute and Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois 60637 [A. J. W., N. H.]
The Bcl-2 protein coded by the proto-oncogene bcl-2 is expressed in a variety of embryonic and postnatal tissues and is overproduced in several types of tumors. Bcl-2 expression suppresses apoptosis induced by a multitude of stimuli in diverse cell types without exerting significant effects on cell proliferation, and is believed to contribute to oncogenesis by extending cell survival. In certain B-cell lymphomas, chromosomal translocations result in a gain of function of Bcl-2 by overexpression. Here, we report that a deletion of a nonconserved region of human Bcl-2 (residues 51–85) confers a novel gain of function that not only supporesses apoptosis induced by the tumor suppressor protein p53 and the Myc oncoprotein but also permits continued cell proliferation. Our result raises the possibility that mutations within the bcl-2 gene may contribute to oncogenesis by both suppressing apoptosis and facilitating cell proliferation.
1 This research was supported by Research Grants CA-33616 and Ca-31719 from the National Cancer Institute (G. C.), and Grant CB-133 from the American Cancer Society and Grants CA-58073 and CA-66132 from the National Cancer Institute (N. H.).
2 To whom requests for reprints should be addressed. Phone: (314) 577-8416; Fax: (314) 577-8406.
Received 2/19/96. Accepted 4/17/96.
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