Inhibition of Fas-induced apoptosis by Bcl-2

Oncogene. 1998 Nov 19;17(20):2549-54. doi: 10.1038/sj.onc.1202192.

Abstract

Jurkat cells express Fas, and rapidly undergo apoptosis in response to Fas ligand or an agonistic anti-Fas antibody. This apoptotic pathway is mediated by a cascade of caspases. In this report, we show that Fas activation induced the processing of caspase 8 in Jurkat cells with a time frame similar to the activation of caspase 3 and the proteolysis of nuclear proteins. Jurkat cell transformants that overexpress Bcl-2 were partially but not completely resistant to the Fas-induced apoptosis. Little processing of caspase 8 was observed upon Fas activation in these transformants. Furthermore, although caspase 8 was recruited to Fas upon Fas activation in the parental Jurkat cells, the recruitment of caspase 8 to Fas was inhibited in the transformants overexpressing Bcl-2. These results suggest that Bcl-2 inhibits Fas-induced apoptosis by preventing the formation of the death-inducing signaling complex that is composed of Fas, FADD/MORT1, and caspase 8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Biological Transport
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • Fas Ligand Protein
  • Genes, bcl-2
  • Humans
  • Jurkat Cells
  • Macromolecular Substances
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / physiology
  • Mice
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Recombinant Fusion Proteins / physiology
  • Transfection
  • fas Receptor / drug effects*
  • fas Receptor / physiology

Substances

  • Enzyme Precursors
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • fas Receptor
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases