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REVIEW: Kinase mTOR: Regulation and Role in Maintenance of Cellular Homeostasis, Tumor Development, and Aging

A. A. Parkhitko1*, O. O. Favorova2, D. I. Khabibullin3, V. N. Anisimov4, and E. P. Henske3

1Department of Genetics, Harvard Medical School, Louis Pasteur Avenue 77, 02155, Boston, USA; E-mail: parhitko@mail.ru

2Pirogov Russian National Research Medical University, Department of Molecular Biology and Medical Biotechnology, ul. Ostrovityanova 1, 117997 Moscow, Russia; fax: (495) 434-6129

3Brigham and Women’s Hospital, Harvard Medical School, Blackfan Circle 1, 02115, Boston, USA; fax: 617-355-9016

4Petrov Research Institute of Oncology, Department of Carcinogenesis and Oncogerontology, ul. Leningradskaya 68, 197758 St. Petersburg, Russia; fax: (812) 436-9567

* To whom correspondence should be addressed.

Received October 20, 2013; Revision received November 19, 2013
Serine/threonine protein kinase mTOR regulates the maintenance of cellular homeostasis by coordinating transcription, translation, metabolism, and autophagy with availability of amino acids, growth factors, ATP, and oxygen. The mTOR kinase is a component of two protein complexes, mTORC1 and mTORC2, which are different in their composition and regulate different cellular processes. An uncontrolled activation of the mTOR kinase is observed in cells of the majority of tumors, as well as in diabetes and neurodegenerative and some other diseases. At present, inhibitors of the kinase complex mTORC1 are undergoing clinical trials. This review focuses on different aspects of the regulation of the mTORC1 and mTORC2 complexes, on their role in the regulation of protein synthesis, metabolism, and autophagy, as well as on using mTOR inhibitors for treatment of tumors and slowing of aging.
KEY WORDS: serine/threonine protein kinase mTOR, mTORC1, mTORC2, rapamycin, autophagy, metabolism, homeostasis, tumor treatment, aging

DOI: 10.1134/S0006297914020023