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mTORC1‐mediated amino acid signaling is critical for cell fate determination under transplant‐induced stress
Author(s) -
Cheng Xiaoyan,
Ge Maolin,
Zhu Shouhai,
Li Dan,
Wang Ruiheng,
Xu Qiongyu,
Chen Zhihong,
Xie Shufeng,
Liu Han
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14008
Subject(s) - mtorc1 , cycloheximide , transplantation , amino acid , autophagy , unfolded protein response , pi3k/akt/mtor pathway , microbiology and biotechnology , protein biosynthesis , mapk/erk pathway , biology , chemistry , signal transduction , biochemistry , medicine , apoptosis , endoplasmic reticulum
Transplantation of in vitro ‐manipulated cells is widely used in hematology. While transplantation is well recognized to impose severe stress on transplanted cells, the nature of transplant‐induced stress remains elusive. Here, we propose that the lack of amino acids in serum is the major cause of transplant‐induced stress. Mechanistically, amino acid deficiency decreases protein synthesis and nutrient consummation. However, in cells with overactive AKT and ERK, mTORC1 is not inhibited and protein synthesis remains relatively high. This impaired signaling causes nutrient depletion, cell cycle block, and eventually autophagy and cell death, which can be inhibited by cycloheximide or mTORC1 inhibitors. Thus, mTORC1‐mediated amino acid signaling is critical in cell fate determination under transplant‐induced stress, and protein synthesis inhibition can improve transplantation efficiency.