E1A-induced processing of procaspase-8 can occur independently of FADD and is inhibited by Bcl-2.
Expression of the 243-residue form of the adenovirus E1A protein in the absence of other viral proteins triggers apoptosis by a pathway that requires p53. This pathway includes processing and activation of initiator procaspase-8, redistribution of cytochrome c, and activation of procaspase-3. Bcl-2 functions at or upstream of procaspase-8 processing to inhibit all of these events and prevent cell death. This contrasts with the anti-apoptotic influence of Bcl-2 family proteins in the cell death pathway induced by Fas ligand or tumor necrosis factor (TNF), in which Bcl-2 typically acts downstream of Fas/TNFR1-mediated activation of caspase-8. Moreover, E1A induces procaspase-8 processing and cell death in cells deleted of FADD, an adaptor protein critical for Fas/TNFR1 activation of caspase-8. The results indicate that E1A is capable of activating caspase-8 by a Bcl-2-inhibitable pathway that does not involve autocrine stimulation of FADD-dependent death receptor pathways.
Nguyen
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M
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Branton
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PE
Roy
S
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Nicholson
D W
DW
Alnemri
E S
ES
Yeh
W C
WC
Mak
T W
TW
Shore
G C
GC
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D029681:Arabidopsis Proteins; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002384:Catalysis; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D010940:Plant Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D029681:Arabidopsis Proteins; D003574:Cytochrome c Group; D004792:Enzyme Precursors; D010940:Plant Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases