Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells

Cancer Lett. 2009 Feb 8;274(1):95-100. doi: 10.1016/j.canlet.2008.09.004. Epub 2008 Oct 7.


Autophagy is a catabolic process involved in cell death and in cell protective mechanism. Autophagic cell death is differentiated from apoptosis by the presence of double or multiple-membrane enclosed vesicles, and the ATG proteins are essential for the formation of these autophagic vesicles. Here, we show that ATG6/Beclin-1 is a novel caspase substrate. ATG6 is directly cleaved by caspases in a process inhibited by the pan caspase inhibitor, zVAD. Ectopic expression of ATG6 suppresses cell death while reduction of ATG6 levels by siRNA sensitizes cells to TRAIL-induced cell death. Also, the inhibition of caspases leads to an increase in autophagy. These results suggest that caspase-mediated cleavage of ATG6 links the apoptotic and autophagic signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy*
  • Beclin-1
  • Blotting, Western
  • Caspase 3 / metabolism*
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • RNA, Small Interfering / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Transfection


  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Enzyme Inhibitors
  • Membrane Proteins
  • RNA, Small Interfering
  • TNF-Related Apoptosis-Inducing Ligand
  • Caspase 3