Ultraviolet Radiation-induced Apoptosis Is Mediated by Activation of CD-95 (Fas/APO-1)*
- From the Departments of ‡Radiation Oncology and§Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109
Abstract
Exposure to ultraviolet light (UV) can induce apoptosis in mammalian cells. The mechanism by which UV radiation engages the suicide apparatus is unclear. Here we demonstrate that UV radiation can activate the Fas pathway via receptor aggregation and subsequent recruitment of the death adaptor molecule FADD/MORT1. UV radiation-induced apoptosis was inhibited by both a dominant negative version of FADD (FADD-DN) and the caspase inhibitor CrmA. Thus, activation of the Fas pathway represents a physiologic mechanism by which UV-damaged cells are eliminated.
Footnotes
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↵* This work was partly supported by a Michigan Memorial-Phoenix Project award (to A. R.).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.
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↵¶ Fellow of the Medical Scientist Training Program supported by the Experimental Immunopathology Training Grant NIGMS T32.
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↵‖ To whom correspondence should be addressed: Dept. of Pathology, University of Michigan Medical School, 1301 Catherine St. Box 0602, Ann Arbor, MI 48109. Tel.: 313-647-2921; Fax: 313-764-4308; E-mail: vmdixit{at}umich.edu.
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↵1 The abbreviations used are: IL, interleukin; TNF-α, tumor necrosis factor α; EGF, epidermal growth factor; FADD-DN, dominant negative version of FADD; PBS, phosphate-buffered saline; PFGE, pulse field gel electrophoresis.
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- Received June 23, 1997.
