p53-Mediated apoptosis is attenuated in Werner syndrome cells
- Elisa A. Spillare,
- Ana I. Robles,
- Xin Wei Wang,
- Jiang-Cheng Shen,
- Chang-Eu Yu,
- Gerard D. Schellenberg, and
- Curtis C. Harris
- Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255 USA; Department of Pathology, University of Washington, Seattle, Washington 98195-7705 USA; Geriatric Research Education and Clinical Center (182B), Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, Washington 98108 USA.
Abstract
The WRN DNA helicase is a member of the DExH-containing DNA helicase superfamily that includes XPB, XPD, and BLM. Mutations in WRN are found in patients with the premature aging and cancer susceptibility syndrome known as Werner syndrome (WS). p53 binds to the WRN protein in vivo and in vitro through its carboxyl terminus. WS fibroblasts have an attenuated p53- mediated apoptotic response, and this deficiency can be rescued by expression of wild-type WRN. These data support the hypothesis that p53 can induce apoptosis through the modulation of specific DExH-containing DNA helicases and may have implications for the cancer predisposition observed in WS patients.
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Footnotes
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↵Corresponding author.
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E-MAIL Curtis_Harris{at}nih.gov; FAX (301) 496-0497.
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- Received February 12, 1999.
- Accepted April 21, 1999.
- Cold Spring Harbor Laboratory Press
