Journal Article

Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle

Margit Rosner, Christiane Fuchs, Nicol Siegel, Alessandro Valli and Markus Hengstschläger

in Human Molecular Genetics

Volume 18, issue 17, pages 3298-3310
Published in print September 2009 | ISSN: 0964-6906
Published online June 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp271
Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle

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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 remains 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.

Journal Article.  8101 words.  Illustrated.

Subjects: Genetics and Genomics

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