Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death

J Biol Chem. 1996 Jul 12;271(28):16510-4. doi: 10.1074/jbc.271.28.16510.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Drosophila
  • Enzyme Inhibitors / pharmacology*
  • Heat-Shock Proteins / physiology*
  • Humans
  • Mice
  • Protein Kinase C / antagonists & inhibitors
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / physiology
  • Staurosporine

Substances

  • Alkaloids
  • Enzyme Inhibitors
  • Heat-Shock Proteins
  • Receptors, Cell Surface
  • Protein Kinase C
  • Staurosporine