P58IPK, a novel cochaperone containing tetratricopeptide repeats and a J-domain with oncogenic potential

Abstract.

Tetratricopeptide repeats (TPRs) are loosely conserved 34-amino acid sequence motifs that have been shown to function as scaffolding structures to mediate protein-protein interactions. TPRs have been identified in a number of proteins with diverse functions and cellular locations. Recent studies suggest that individual TPR motifs can confer specificity in promoting homotypic and/or heterotypic interactions, often in a mutually exclusive manner. These features are best exemplified by the P58^IPK protein, an influenza virus-activated cellular inhibitor of the PKR protein kinase, whose different TPR motifs mediate interactions with distinct proteins. P58^IPK, which possesses cochaperone and oncogenic properties, represents a unique class of TPR proteins containing a J-domain. Here we review recent progress on the structural and functional characterization of P58^IPK, and discuss the possible mechanisms by which P58^IPK modulates PKR and induces tumorigenesis in view of present knowledge of TPR proteins and molecular chaperones.