Inhibition of Daxx-mediated apoptosis by heat shock protein 27.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Chloromethyl Ketones, Antigens, CD95, Apoptosis, Arabidopsis Proteins, Binding Sites, Carrier Proteins, Caspases, Cell Differentiation, Cell Line, Cell Nucleus, Cytoplasm, Dimerization, Fas-Associated Death Domain Protein, Heat-Shock Proteins, Humans, Intracellular Signaling Peptides and Proteins, Kinetics, Microscopy, Fluorescence, Mutation, Nuclear Proteins, Phosphorylation, Plant Proteins, Protein Binding, Protein Transport, Signal Transduction, Transfection, Two-Hybrid System Techniques
Mol. Cell. Biol.
Date: Oct. 01, 2000
Download Curated Data For This Publication
146972
Switch View:
  • Interactions 4