Regulatable expression of the interferon-induced double-stranded RNA dependent protein kinase PKR induces apoptosis and Fas receptor expression

PKR is an interferon-induced dsRNA-dependent protein kinase involved in the antiviral response as well as in cell growth and differentiation. Studies using a transdominant negative mutant of PKR also have implicated the kinase in tumor suppression and apoptosis. However, functional studies of PKR have been hampered by the lack of a suitable expression system, in this study, we used a tetracycline-regulated inducible system in NIH3T3 cells to investigate the Involvement of PKR in programmed cell death (apoptosis). We show that expression of wild-type PKR causes apoptosis and correlates with increased mRNA levels for the Fas receptor, a member of the tumor necrosis family of proteins. Expression of an inactive form of PKR (K296R) or the vector alone did not induce apoptosis or elevate Fas mRNA levels. Our results clearly demonstrate that expression of an active form of PKR triggers apoptosis, possibly through upregulation of the Fas receptor. (C) 1999 Academic Press.