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Current Genetics

, Volume 64, Issue 5, pp 965–970 | Cite as

Branching the Tel2 pathway for exact fit on phosphatidylinositol 3-kinase-related kinases

  • Katsunori Sugimoto
Review
  • 270 Downloads

Abstract

Phosphatidylinositol 3-kinase-related kinases (PIKKs), are structurally related to phosphatidylinositol 3-kinase (lipid kinase), but possess protein kinase activities. PIKKs include ATM, ATR, DNA-PK, mTOR and SMG1, key regulators of cell proliferation and genome maintenance. TRRAP, which is devoid of protein kinase activity, is the sixth member of the PIKK family. PIKK family members are gigantic proteins in the range of 300–500 kDa. It has become apparent in the last decade that the stability or maturation of the PIKK family members depends on a molecular chaperone called the Tel2-Tti1-Tti2 (TTT) complex. Several lines of evidence have established a model in which TTT connects to the Hsp90 chaperone through the Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex in mammalian and yeast cells. However, recent studies of yeast cells indicate that TTT is able to form different complexes. These observations raise a possibility that several different mechanisms regulate TTT-mediated protein stability of PIKKs.

Keywords

Protein folding Mec1 Tel1 Casein kinase Asa1 Cdc37 

Notes

Acknowledgements

I thank John Kang, Hisao Masukata and Carol Newlon for helpful comments.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Microbiology, Biochemistry and Molecular Genetics, International Center for Public Health, New Jersey Medical School, RutgersThe State University of New JerseyNewarkUSA

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