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PMID: 22540023 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2.

Nucleus (Austin, Tex.) ·Vol. 3 ·No. 1 ·2012-00-00 ·Pages 29-43

Izumi N, Yamashita A, Ohno S

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.

Keywords
AAA+ ATM ATR DNA damage response DNA-PKcs PIKK RUVBL SMG-1 TRRAP mTOR
MeSH Terms
Adenosine Triphosphatases/metabolism Animals DNA Helicases/metabolism Humans Molecular Chaperones/metabolism Phosphatidylinositol 3-Kinases/metabolism Protein Kinases/metabolism Stress, Physiological
Chemicals
Molecular Chaperones Protein Kinases Phosphatidylinositol 3-Kinases Adenosine Triphosphatases DNA Helicases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Izumi Natsuko
Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama, Japan.
Yamashita Akio
Ohno Shigeo
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Article Info
Journal
Nucleus (Austin, Tex.)
Abbr.
Nucleus
ISSN
1949-1042
DOI
10.4161/nucl.18926
Published
2012-00-00
Pages
29-43
Language
English
Region
United States
NLM ID
101518322
PMCID
PMC3337166
Subset
IM
External Links
PubMed source DOI: 10.4161/nucl.18926 PMC Full Text View journal details
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