Interaction of the adenovirus 14.7-kDa protein with FLICE inhibits Fas ligand-induced apoptosis

Abstract

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 re- suited 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-1β-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.