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Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8
Li Yu,1Ajjai Alva,2Helen Su,1Parmesh Dutt,1Eric Freundt,1,3Sarah Welsh,1Eric H. Baehrecke,2Michael J. Lenardo1*
Caspases play a central role in apoptosis, a well-studied pathwayof programmed cell death. Other programs of death potentiallyinvolving necrosis and autophagy may exist, but their relationto apoptosis and mechanisms of regulation remains unclear. Wedefine a new molecular pathway in which activation of the receptor-interactingprotein (a serine-threonine kinase) and Jun amino-terminal kinaseinduced cell death with the morphology of autophagy. Autophagicdeath required the genes ATG7 and beclin 1 and was induced bycaspase-8 inhibition. Clinical therapies involving caspase inhibitorsmay arrest apoptosis but also have the unanticipated effectof promoting autophagic cell death.
1 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 2 Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, MD 20742, USA. 3 Weatherall Institute of Molecular Medicine, Oxford University, Headington, Oxford OX39D, UK.
* To whom correspondence should be addressed. E-mail: lenardo{at}nih.gov
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Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells.
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Selective Inactivation of a Fas-associated Death Domain Protein (FADD)-dependent Apoptosis and Autophagy Pathway in Immortal Epithelial Cells.
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Mol. Biol. Cell
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