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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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|Abstract »|Full Text »|PDF »
Autophagy Gene Disruption Reveals a Non-vacuolar Cell Death Pathway in Dictyostelium.
A. Kosta, C. Roisin-Bouffay, M.-F. Luciani, G. P. Otto, R. H. Kessin, and P. Golstein (2004)
J. Biol. Chem.
279, 48404-48409
|Abstract »|Full Text »|PDF »
Autophagy in Health and Disease: A Double-Edged Sword.
