Microphthalmia-associated transcription factors activate mTORC1 through RagD GTPase gene expression

The mechanistic target of rapamycin complex 1 (mTORC1) is a major serine/threonine kinase that stimulates cellular anabolic processes including protein and lipid synthesis while suppressing catabolic processes such as autophagy in response to growth factors and amino acids (1). Upon mTORC1 activation, it phosphorylates multiple substrates including S6 kinase (S6K), eIF4E binding protein (4EBP), and unc-51-like kinase (ULK) (2). Both S6K and 4EBP are key regulators for mRNA translation and cell cycle progression (3). In addition to mTORC1’s roles in stimulating these anabolic processes, mTORC1-dependent ULK phosphorylation inhibits its kinase activity, which is essential for autophagy induction (4). Thus, mTORC1 activation in response to growth factors and amino acids promotes key cellular anabolic processes while it suppresses major catabolic processes, to build biosynthetic molecules essential for cell growth and proliferation.