Cleaving Beclin 1 to suppress autophagy in chemotherapy-induced apoptosis

Autophagy. 2011 Oct;7(10):1239-41. doi: 10.4161/auto.7.10.16490. Epub 2011 Oct 1.

Abstract

Autophagy is often found in apoptosis-defective cancer cells and contributes to chemotherapy resistance. However, it is far from clear how the coordination of apoptosis and autophagy determines sensitivity of cancer cells to chemotherapy. Our recent study showed that Beclin 1, a key regulator of autophagy, is cleaved by caspase 8 at the execution stage of chemotherapy-induced and mitochondria-mediated apoptosis. Perturbation of Beclin 1 cleavage, by knock-in of a mutation, phenocopies the autophagy observed in apoptosis-defective cancer cells, and renders chemotherapy resistance in vitro and in vivo. These results demonstrate an important role of caspases in suppressing autophagy by cleaving autophagic machinery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Apoptosis Regulatory Proteins / chemistry*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy*
  • Beclin-1
  • Caspase 8 / metabolism
  • Cytochromes c / metabolism
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / metabolism
  • Models, Biological
  • Mutation

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • light chain 3, human
  • Cytochromes c
  • Caspase 8