title: Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death.
abstract: Small stress protein expression enhances the survival of mammalian cells exposed to numerous injuries that induce necrotic cell death. The cell surface receptor Fas/APO-1 and its ligand have been recently identified as important mediators of apoptosis. Here, we show that constitutive expression of human heat shock protein (hsp)27 in murine L929 cells blocks Fas/APO-1-mediated cell death. Expression of human hsp27 prevented anti-APO-1-induced DNA fragmentation and morphological changes. These results strongly suggest that human hsp27 acts as a cellular inhibitor of Fas/APO-1-induced apoptosis. We also report that the expression of small stress proteins from different species, such as human hsp27, Drosophila Dhsp27, or human alphaB-crystallin, confers resistance to apoptotic cell death induced by staurosporine, a protein kinase C inhibitor. Hence, small stress proteins are novel regulators that are able to block apoptosis induced by different pathways.
authors.affiliation: Laboratoire du Stress Cellulaire, Centre de Génétique Moléculaire et Cellulaire, CNRS UMR-5534, Université Claude Bernard Lyon-I, 69622 Villeurbanne, France.
authors.forename: P
authors.initials: P
authors.lastname: Mehlen
authors.forename: K
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: A P
authors.initials: AP
authors.lastname: Arrigo
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004330:Drosophila; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000502:physiology; D019311:Staurosporine
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D011956:Receptors, Cell Surface; D011493:Protein Kinase C; D019311:Staurosporine