Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8
Abstract
Caspases play a central role in apoptosis, a well-studied pathway of programmed cell death. Other programs of death potentially involving necrosis and autophagy may exist, but their relation to apoptosis and mechanisms of regulation remains unclear. We define a new molecular pathway in which activation of the receptor-interacting protein (a serine-threonine kinase) and Jun amino-terminal kinase induced cell death with the morphology of autophagy. Autophagic death required the genes ATG7 and beclin 1 and was induced by caspase-8 inhibition. Clinical therapies involving caspase inhibitors may arrest apoptosis but also have the unanticipated effect of promoting autophagic cell death.
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The authors thank T. Maugel for assistance with TEM and R. Siegel, J. Puck, L. Zheng, S. Straus, and D. Douek for comments on the manuscript. E.F. is an NIH–Oxford University Scholar in Biomedical Research. H.S. is a Fellow of Cancer Research Institute. This work was supported by NIH grant GM59136 (E.H.B.).
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Science
Volume 304 | Issue 5676
4 June 2004
4 June 2004
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American Association for the Advancement of Science.
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Received: 10 February 2004
Accepted: 28 April 2004
Published in print: 4 June 2004
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