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TOR signaling and control of cell growth
Author(s) -
Hall Michael N
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a206-c
Subject(s) - tor signaling , ribosome biogenesis , mtorc1 , biology , microbiology and biotechnology , mtorc2 , pi3k/akt/mtor pathway , nutrient sensing , biogenesis , mechanistic target of rapamycin , cell growth , saccharomyces cerevisiae , yeast , model organism , signal transduction , autophagy , ribosome , genetics , gene , rna , apoptosis
TOR (target of rapamycin) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress (1). TOR was originally discovered in yeast, but has since been shown to be conserved in all eukaryotes including yeast, plants, worms, flies, and mammals. The discovery of TOR led to a fundamental change in how one thinks of cell growth. It is not a spontaneous process that simply happens when building blocks (nutrients) are available, but rather is a highly regulated, plastic process that is controlled by TOR‐dependent signaling pathways. TOR is found in two structurally and functionally distinct multiprotein complexes, TORC1 and TORC2. The two TOR complexes, like TOR itself, are highly conserved. Yeast TORC1 is rapamycin sensitive, and contains KOG1, LST8 and either TOR1 or TOR2. The mammalian counterpart of TORC1, mTORC1, contains raptor (mKOG1), mLST8, and mTOR. TORC1 in yeast and mammals mediates temporal control of cell growth by regulating several cellular processes including translation, transcription, ribosome biogenesis, nutrient transport and autophagy. Yeast TORC2 is rapamycin insensitive, and contains AVO1, AVO2, AVO3, BIT61, LST8, and TOR2. mTORC2 is also rapamycin insensitive and contains SIN1 (mAVO1), rictor (mAVO3), mLST8, and mTOR. TORC2 in yeast and mammals mediates spatial control of cell growth by regulating the actin cytoskeleton. Thus, the two TOR complexes constitute an ancestral signaling network conserved throughout eukaryotic evolution to control the fundamental process of cell growth. The physiological consequences of mTORC1 dysregulation suggest that inhibitors of mTOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders. The study of TOR signaling demonstrates the value of model organisms in biomedical research. Data on the role of mTORC1 and mTORC2 in specific tissues will be presented.