Human Molecular Genetics Advance Access published online on June 8, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp271
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Functional interaction of mTOR complexes in regulating mammalian cell size and cell cycle
Medical Genetics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
* To whom correspondence should be addressed: Markus Hengstschläger, PhD, Prof, Medical Genetics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Tel: +43/1/40400/7847, FAX: +43/1/40400/7848, E-mail: markus.hengstschlaeger{at}meduniwien.ac.at
Received May 14, 2009; Revised May 14, 2009; Accepted June 4, 2009
Dysregulation of the mammalian target of rapamycin (mTOR) kinase pathway is centrally involved in a wide variety of cancers and human genetic diseases. In mammalian cells mTOR is part of two different kinase complexes, mTORC1 composed of mTOR, raptor and mLST8, and mTORC2 containing mTOR, rictor, Sin1 and mLST8. Whereas, mTORC1 is known to be a pivotal regulator of cell size and cell cycle control, the question whether the recently discovered mTORC2 complex is involved in these processes remained elusive. We report here that the mTORC1-mediated consequences on cell cycle and cell size are separable and do not involve effects on mTORC2 activity. However, we show that mTORC2 itself is a potent regulator of mammalian cell size and cell cycle via a mechanism involving the Akt/TSC2/Rheb cascade. Our data are of relevance for the understanding of the molecular development of the many human diseases caused by deregulation of upstream and downstream effectors of mTOR.