SMALL STRESS PROTEINS AS NOVEL REGULATORS OF APOPTOSIS - HEAT-SHOCK PROTEIN-27 BLOCKS FAS APO-1-INDUCED AND STAUROSPORINE-INDUCED CELL-DEATH/

Small stress protein expression enhances the survival of mammalian cel ls exposed to numerous injuries that induce necrotic cell death. The c ell surface receptor Fas/APO-1 and its ligand have been recently ident ified as important mediators of apoptosis. Here, we show that constitu tive expression of human heat shock protein (hsp)27 in murine L929 cel ls blocks Fas/APO-1-mediated cell death. Expression of human hsp27 pre vented anti-APO-1-induced DNA fragmentation and morphological changes. These results strongly suggest that human hsp27 acts as a cellular in hibitor of Fas/APO-1-induced apoptosis. We also report that the expres sion of small stress proteins from different species, such as human hs p27, Drosophila Dhsp27, or human alpha B-crystallin, confers resistanc e 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.