title: Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2.
abstract: Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative "PIKK regulatory chaperone complex" including other PIKK regulators, Hsp90 and the Tel2 complex.
authors.affiliation: Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Izumi
authors.forename: Akio
authors.initials: A
authors.lastname: Yamashita
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D004265:DNA Helicases / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D018832:Molecular Chaperones; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases