Fig. 3.

MYC regulation: an example of how feedback among protein synthesis, cell metabolism, and protein degradation controls T cell function. Under high nutrient environments and/or high pro-growth signaling, there are high levels of amino acid and glucose uptake. This fuels high energy (ATP) production, supporting high levels of protein synthesis and the production of UDP-GlcNAc from glutamine and glucose. O-GlcNAcylation at Thr58 stabilizes MYC and prevents its proteasomal degradation. Increased MYC expression promotes the transcription of mRNA for the synthesis of proteins, including amino acid transporters, metabolic enzymes, and ribosomes, thus creating a positive feedforward loop to support a highly biosynthetic environment and sustain high MYC expression. This environment supports the high expression of effector proteins. In contrast, in low nutrient conditions and/or low pro-growth signaling, there is low amino acid and glucose uptake. This results in low energy production and limited fuel and biomolecules for the synthesis of effector proteins. Less MYC is synthesized, and thus, less MYC is O-GlcNAcylated, increasing the proteasomal degradation of MYC. This feedback reduces the MYC-mediated transcription of pro-growth mRNAs