Interaction of the adenovirus 14.7-kDa protein with FLICE inhibits Fas ligand-induced apoptosis.
Adenovirus type 5 encodes a 14.7-kDa protein that protects infected cells from tumor necrosis factor-induced cytolysis by an unknown mechanism. In this report, we demonstrate that infection of cells with an adenovirus vector expressing Fas ligand induced rapid apoptosis that was blocked by coinfection with a virus expressing 14. 7K. Moreover, AdFasL/G infection resulted in the rapid activation of DEVD-specific caspases, and caspase activation was blocked by coinfection with Ad14.7/G. Cell death induced by the overexpression of Fas ligand, Fas-associated death domain-containing protein (FADD)/MORT1, or FADD-like interleukin-1beta-converting enzyme (FLICE)/caspase-8 in a virus-free system was efficiently blocked by 14.7K expression. Moreover, we demonstrate that 14.7K interacts with FLICE. These results support the idea that FLICE is a cellular target for the 14.7-kDa protein.
Chen
P
P
GenVec, Inc., Rockville, Maryland 20852, USA.
Tian
J
J
Kovesdi
I
I
Bruder
J T
JT
D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000737:chemistry*; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D020170:Caspase 1; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D015870:Gene Expression / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D015843:Serpins / Q000378:metabolism; D014162:Transfection / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; D011065:Poly(ADP-ribose) Polymerases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1