p58(IPK), novel cochaperone containing tetratricopeptide repeats and a J-domain with oncogenic potential

Tetratricopeptide repeats (TPRs) are loosely conserved 34-amino acid sequen ce motifs that have been shown to function as scaffolding structures to med iate protein-protein interactions. TPRs have been identified in a number of proteins with diverse functions and cellular locations. Recent studies sug gest that individual TPR motifs can confer specificity in promoting homotyp ic and/or heterotypic interactions, often in a mutually exclusive manner. T hese features are best exemplified by the P58(IPK) protein, an influenza vi rus-activated cellular inhibitor of the PKR protein kinase, whose different TPR motifs mediate interactions with distinct proteins. P58(IPK), which po ssesses cochaperone and oncogenic properties, represents a unique class of TPR proteins containing a J-domain. Here we review recent progress on the s tructural and functional characterization of p58(IPK), and discuss the poss ible mechanisms by which P58(IPK) modulates PKR and induces tumorigenesis i n view of present knowledge of TPR proteins and molecular chaperones.