Interaction of Beclin 1 with survivin regulates sensitivity of human glioma cells to TRAIL-induced apoptosis

FEBS Lett. 2010 Aug 20;584(16):3519-24. doi: 10.1016/j.febslet.2010.07.018. Epub 2010 Jul 16.

Abstract

We reported a novel interaction between Beclin 1, a key regulator of autophagy, and survivin, a member of the inhibitor of apoptosis protein family. We found that knock-down of Beclin 1 down-regulated survivin protein, and the turnover rate of survivin was increased when Beclin 1 expression was silenced. Knock-down of Beclin 1 sensitized glioma cells to TRAIL-induced apoptosis, and introduction of survivin antagonized the sensitizing effect, suggesting that down-regulation of survivin mediates the enhanced sensitivity to TRAIL-induced apoptosis. These results demonstrate a novel interaction between Beclin 1 and survivin, and may provide a potential mechanism underlying the cross-talk between autophagy and apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Base Sequence
  • Beclin-1
  • Cell Line, Tumor
  • DNA Primers / genetics
  • Down-Regulation
  • Gene Knockdown Techniques
  • Glioma / drug therapy
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Protein Interaction Mapping
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • BIRC5 protein, human
  • Beclin-1
  • DNA Primers
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human