Abstract
Fas is a member of the tumor necrosis factor receptor family that can induce apoptosis by the recruitment and activation of caspase-8 (formerly called FLICE, MACH or MCH-5). Recently, caspase-8/FLICE inhibitory proteins (FLIPs) have been identified as proteins that counteract the caspase-8-dependent apoptosis-promoting activity of Fas and other death receptors. Viral and cellular FLIPs, which share structural similarity with caspase-8, are recruited to the death receptors upon ligand binding and inhibit caspase-8 activation. Viral FLIP family members are present in several lymphotropic herpesviruses and in a human poxvirus, and expression of viral FLIP proteins is thought to prevent or delay the elimination of virus-infected cells by cytotoxic T cells. Cellular FLIP has a similar anti-apoptotic function, but genetic studies have revealed additional, previously unanticipated roles in T-cell proliferation and heart development. Moreover, abnormal expression of cellular FLIP may play a role in autoimmune diseases, in tumor development and in cardiovascular disorders.
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