Cell Cycle Regulation by the Nutrient-Sensing Mammalian target of rapamycin (mTOR) pathway

Abstract

Cell division involves a series of ordered and controlled events that lead to cell proliferation. Cell cycle progression implies not only demanding amounts of cell mass, protein, lipid, and nucleic acid content but also a favorable energy state. The mammalian target of rapamycin (mTOR), in response to the energy state, nutrient status, and growth factor stimulation of cells, plays a pivotal role in the coordination of cell growth and the cell cycle. Here, we review how the nutrient-sensing mTOR-signaling cascade molecularly integrates nutritional and mitogenic/anti-apoptotic cues to accurately coordinate cell growth and cell cycle. First, we briefl y outline the structure, functions, and regulation of the mTOR complexes (mTORC1 and mTORC2). Second, we concisely evaluate the best known ability of mTOR to control G1-phase progression. Third, we discuss in detail the recent evidence that indicates a new genome stability caretaker function of mTOR based on the specifi c ability of phosphorylated forms of several mTOR-signaling components (AMPK, raptor, TSC, mTOR, and S6K1), which spatially and temporally associate with essential mitotic regulators at the mitotic spindle and at the cytokinetic cleavage furrow.