Chapter 8 - mTORC1 and Cell Cycle Control

Abstract

I. Abstract Target of rapamycin (TOR) proteins play key roles in regulating cellular functions in eukaryotes. They form signaling complexes with partner proteins and respond to nutritional, hormonal, and other cues. It is now clear that TOR proteins can control several stages of the cell cycle, although the mechanisms by which they do this appear to differ considerably between different organisms. In budding yeast, TOR complex 1 (TORC1) promotes exit of cells from a quiescent state known as G 0 . In mammals, and likely in many other species, (m)TORC1 promotes progression of cells from G1 into S-phase, for example, by regulating the levels of specific cyclins and thus the activity of cyclin-dependent kinases. mTORC1 may also influence this step of the cell cycle through its control of mitochondrial function and/or ribosome biogenesis. Recent data from diverse organisms also identify roles for TOR proteins in G2 progression and/or M-phase entry, although in different systems TOR signaling may promote or retard M-phase entry. These effects on cell cycle underlie the utility of rapamycin (and related compounds) which inhibit mTORC1 as immunosuppressants and the potential value of such reagents as anticancer drugs. Existing data are stimulating further studies to elucidate the intricate web of regulatory processes through which TOR proteins control cell size and cell proliferation and may lead to further developments in the use of TOR inhibitors as therapeutic agents.