期刊
NUCLEUS
卷 3, 期 1, 页码 29-43出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/nucl.18926
关键词
PIKK; ATM; ATR; DNA-PKcs; mTOR; SMG-1; TRRAP; AAA; RUVBL; DNA damage response
类别
资金
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Science and Technology Corporation
- Takeda Science Foundation
- Mitsubishi foundation
- Uehara memorial foundation
- Yokohama Foundation for Advancement of Medical Science
- Grants-in-Aid for Scientific Research [22247030, 23687025] Funding Source: KAKEN
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.
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