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Molecular and Cellular Biology, October 2000, p. 7602-7612, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Inhibition of Daxx-Mediated Apoptosis by Heat Shock Protein 27

Steve J. Charette, Josée N. Lavoie, Herman Lambert, and Jacques Landry*

Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Québec, Canada G1R 2J6

Received 18 February 2000/Returned for modification 13 April 2000/Accepted 25 July 2000

Heat shock protein 27 (HSP27) confers cellular protection against a variety of cytotoxic stresses and also against physiological stresses associated with growth arrest or receptor-mediated apoptosis. Phosphorylation modulates the activity of HSP27 by causing a major change in the supramolecular organization of the protein, which shifts from oligomers to dimers. Here we show that phosphorylated dimers of HSP27 interact with Daxx, a mediator of Fas-induced apoptosis, preventing the interaction of Daxx with both Ask1 and Fas and blocking Daxx-mediated apoptosis. No such inhibition was observed with an HSP27 phosphorylation mutant that is only expressed as oligomers or when apoptosis was induced by transfection of a Daxx mutant lacking its HSP27 binding domain. HSP27 expression had no effect on Fas-induced FADD- and caspase-dependent apoptosis. However, HSP27 blocked Fas-induced translocation of Daxx from the nucleus to the cytoplasm and Fas-induced Daxx- and Ask1-dependent apoptosis. The observations revealed a new level of regulation of the Fas pathway and suggest a mechanism for the phosphorylation-dependent protective function of HSP27 during stress and differentiation.

* Corresponding author. Mailing address: Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, 9, rue McMahon, Quebec, Canada G1R 2J6. Phone: (418) 525-4444, ext. 5555. Fax: (418) 691-5439. E-mail: jacques.landry{at}med.ulaval.ca.

Molecular and Cellular Biology, October 2000, p. 7602-7612, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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