Canonical signaling and nuclear activity of mTOR—a teamwork effort to regulate metabolism and cell growth

Abstract

Mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates almost all functions related to cell growth and metabolism in response to extra- and intracellular stimuli, such as availability of nutrients, the presence of growth factors, or the energy status of the cell. As part of two distinct protein complexes, mTORC1 and mTORC2, the kinase has been shown to influence cell growth and proliferation by controlling ribosome biogenesis, mRNA translation, carbohydrate and lipid metabolism, protein degradation, autophagy as well as microtubule and actin dynamics. In addition to these well-characterized functions, mTOR can also influence gene transcription. While most studies focused on investigating how canonical mTOR signaling regulates the activity of transcription factors outside the nucleus, recent findings point to a more direct role for mTOR as a transcription factor operating on chromatin in the nucleus. In particular, recent genome-wide identification of mTOR targets on chromatin reveals that its activities in the nucleus and cytoplasm are functionally and biologically linked, thus uncovering a novel paradigm in mTOR function.