mTORC1

Cystine availability regulates mTORC1 signaling

Cystine deprivation resulted in a time-dependent reduction of mTORC1 signaling, as evidenced by the gradual decrease in the phosphorylation of p70S6K (T389) and S6 (S235/236), which are downstream effectors of mTORC1 (Fig. 1A).

Cystine restriction elevated the level of phospho-eIF2α (S51) and ATF4 (Fig. 1A), major nodes of the ISR signaling. Thus, cystine limitation suppressed mTORC1 and activated the ISR, the two major amino acid sensing pathways in HepG2 cells. (R1)

Thus, cystine starvation induces a stress signal of amino acid limitation through GCN2-eIF2α-ATF4 branch in the ISR but not ER stress in HepG2 cells. (R1)

ISR - integrated stress response (Wikipedia) GCN2 - general control nonderepressible 2. See Wikipedia. Gene EIF2AK4 (Uniprot) eIF2α - eukaryotic initiation factor 2α. Heterotrimer: alpha (EIF2S1), beta (EIF2S2), gamma (EIF2S3). ATF4 - Cyclic AMP-dependent transcription factor ATF-4 (Uniprot)