期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 25, 期 -, 页码 1538-1567出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4867
关键词
PIKK; Phosphatidylinositol-3 kinase-related kinases; mTOR; mammalian target of rapamycin; ATR; ATM- and Rad3-related kinase; ATM; Ataxia telangiectasia mutated kinase; DNA-PKcs; DNA dependent protein catalytic subunit; TRRAP; Transformation-transactivation domain-associated protein; hSMG1; Suppressor with morphological effect on genitalia family member; DNA damage response
资金
- Indian Institute of Technology Gandhinagar [SR/FST/CSI-277/2016]
- DST-FIST Department of Science and Technology, India [SR/FST/CSI-277/2016]
Phosphatidylinositol-3 kinase-related kinases (PIKKs) is a class of six unique serine/threonine kinases that are characterized as high molecular mass colossal proteins present in multicellular organisms. They predominantly regulate the innumerable eukaryotic cellular processes, for instance, cell-signaling cascades related to DNA damage and repair, cell growth and proliferation, cell cycle arrest, genome surveillance, gene expression and many other important yet diverse functions. A characteristic PIKK member comprises of an N-terminal HEAT domain, followed by FAT domain, a highly conserved kinase catalytic domain, and a C-terminal FATC domain. In this comprehensive review, we reassess and discuss various established functions of all the six PIKK members with each function corroborated by their structural topology. In addition to the domain architecture of these atypical kinases, their specific inhibitors have been briefly deliberated. This review gives us the impression of the emergent importance of PIKKs, which, despite of their complexity, are the hub of research with respect to the inhibitor development.
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