Smac/DIABLO is required for effector caspase activation during apoptosis in human cells

Apoptosis. 2007 Aug;12(8):1503-10. doi: 10.1007/s10495-007-0067-7.

Abstract

Mitochondria play a pivotal role during stress-induced apoptosis as several proapoptotic proteins are released to the cytosol to activate caspases. Smac/DIABLO is one of the proapoptotic proteins released from the mitochondria and has been shown to inactivate IAPs. However, gene knockout studies in mice revealed a redundant role for Smac during development and cell death. By applying RNA interference-mediated loss of function approach, we demonstrate that Smac/DIABLO is required for the activation of effector but not initiator caspases during stress and receptor-mediated cell death in HeLa cells. Cells with reduced Smac resist apoptosis and retained clonogenicity. Our results suggest an obligatory role for Smac/DIABLO in these tumor cells during several pathways of apoptosis induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Apoptosis* / genetics
  • Brefeldin A / pharmacology
  • Caspases, Effector / metabolism*
  • Enzyme Activation / genetics
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / physiology*
  • Protein Synthesis Inhibitors / pharmacology
  • RNA Interference
  • Transfection

Substances

  • Apoptosis Regulatory Proteins
  • DIABLO protein, human
  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • Protein Synthesis Inhibitors
  • Brefeldin A
  • Caspases, Effector