title: 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 P58IPK protein, an influenza virus-activated cellular inhibitor of the PKR protein kinase, whose different TPR motifs mediate interactions with distinct proteins. P58IPK, 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 P58IPK, and discuss the possible mechanisms by which P58IPK modulates PKR and induces tumorigenesis in view of present knowledge of TPR proteins and molecular chaperones.
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle 98195, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Melville
authors.forename: M G
authors.initials: MG
authors.lastname: Katze
authors.forename: S L
authors.initials: SL
authors.lastname: Tan
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D050956:HSP40 Heat-Shock Proteins; D006801:Humans; D007372:Interferons / Q000502:physiology; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: C494651:DNAJC3 protein, human; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D012097:Repressor Proteins; D007372:Interferons; D019892:eIF-2 Kinase