ONCOGENIC POTENTIAL OF TAR RNA-BINDING PROTEIN TRBP AND ITS REGULATORY INTERACTION WITH RNA-DEPENDENT PROTEIN-KINASE PKR

TAR RNA binding protein (TRBP) belongs to an RNA binding protein famil y that includes the double-stranded RNA-activated protein kinase (PKR) , Drosophila Staufen and Xenopus xlrbpa. One member of this family, PK R, is a serine/threonine kinase which has anti-viral and anti-prolifer ative effects, In this study we show that TRBP is a cellular down-regu lator of PKR function, Assaying expression from an infectious HIV-1 mo lecular clone, we found that PKR inhibited viral protein synthesis and that over-expression of TRBP effectively countered this inhibition. I n intracellular and in cell-free assays we show that TRBP directly inh ibits PKR autophosphorylation through an RNA binding-independent pathw ay. Biologically, TRBP serves a growth-promoting role; cells that over express TRBP exhibit transformed phenotypes. Our results demonstrate t he oncogenic potential of TRBP and are consistent with the notion that intracellular PKR function contributes physiologically towards regula ting cellular proliferation.