Previous Article | Next Article ![]()
Molecular and Cellular Biology, October 2000, p. 7602-7612, Vol. 20, No. 20
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.
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
*
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.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|