Fig. 2

Regulation of mTOR transcription. Amino acids increase mTOR transcription through induction of binding of transcriptional activators such as Nuclear Receptor Co-Activator 5 (NCOA5), Purine-Rich Element Binding Protein B (PURB), cyclin-dependent kinase substrate 1 (NUCKS1), and nuclear factor of kB (NFkB) to the mTOR promoter. In addition, amino acids induce the degradation of AT-rich interaction domain 1 A (ARID1A) and ARID1B, which result in increased mTOR transcription, through relieve of the inhibitory effect of H3K27ac, an epigenetic modified histone that marks for active enhancers; and the reversal of the inhibitory effect of ARID1B on mTOR promoter, respectively. The binding of H3K27ac to mTOR is further regulated by ARID4B and Brahma-related gene 1 (BRG1), that bind themselves to the promoter of mTOR in an amino acid-dependent manner. BRG1 additionally relieves the inhibitory effect of H3K27me3 on mTOR transcription. Other inducers of mTOR transcription upon amino acid stimulation, particularly, taurine, include the epigenetic marker for promoter activation H3K4Me3 and Cullin 5 (Cul5), an ubiquitin ligase that is highly expressed in mammary gland tissues in the lactation stage