FIGURE 3.

mTORC1 integrates and coordinates multiple signals and responses. Conditions: mTORC1 activity is subjected to various cellular conditions, whereby pro-growth triggers (e.g., growth factors, glucose, and amino acids) promote mTORC1, while stress conditions (e.g., DNA damage) abate mTORC1 activity. Regulators: Growth conditions stimulate mTORC1 by (i) arresting the Rheb GAP, TSC, leading to GTP-bound Rheb GAP and (ii) stimulating Rag GTPase GEF complex, Ragulator, leading to GTP-bound RagA/B. See text for additional detail. Among negative regulators, AMPK acts as a major dampener of mTORC1 function by concurrently abating Ragulator and promoting TSC, thus hindering Rag and Rheb GTPases. Effectors and Functions: Active mTORC1 can then phosphorylate a variety of effector proteins. This includes activating S6Ks but blocking 4E-BP proteins, which ultimately promotes protein synthesis by increasing the rate of mRNA translation initiation and elongation, ribosome biogenesis and selective translation of specific mRNAs. mTORC1 also promotes lipid biosynthesis, energy storage and consumption by stimulating lipin-1 and SREBP, which enhance expression and activity of lipid biogenesis enzymes. mTORC1 stimulates Myc among other targets to drive cells towards growth and mitosis. In comparison, mTORC1 blocks ULK1 and TFEB to arrest catabolic and degradative pathways including autophagy and lysosome biogenesis to elicit biomass accumulation.