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

Cleaving Beclin 1 to suppress autophagy in chemotherapy-induced apoptosis.

Author information

1
University of Pittsburgh Cancer Institute, PA, USA.

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.

PMID:
21610315
PMCID:
PMC3210308
DOI:
10.4161/auto.7.10.16490
[Indexed for MEDLINE]
Free PMC Article

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