Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis

• DOI: 10.1038/s41419-021-04417-w
• Publication Date: 2021-12-03T17:03:43Z
• Authors: Hyeon-Ok Jin; Sung-Eun Hong; Ji-Young Kim; Se-Kyeong Jang; In-Chul Park
• Keywords: ATF4

Abstract Amino acid availability is sensed by various signaling molecules, including general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). However, it unclear how these sensors are associated with cancer cell survival under low amino availability. In the present study, we investigated AKT activation in non-small lung (NSCLC) cells deprived each one 20 acids. Among acids, deprivation glutamine, arginine, methionine, lysine induced activation. was GCN2/ATF4/REDD1 axis-mediated mTORC2 deprivation. CRISPR-Cas9-mediated REDD1-knockout cells, not deprivation, indicating that REDD1 plays a major role Knockout sensitized cultured glutamine conditions to radiotherapy. Taken together, axis promotes signal, which might be potential for therapy.