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

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 is unclear how these sensors are associated with cancer cell survival under low amino acid availability....

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Autores principales:	Hyeon-Ok Jin, Sung-Eun Hong, Ji-Young Kim, Se-Kyeong Jang, In-Chul Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/1f5af1fef3a44d8a8f236de5a2388f04
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spelling	oai:doaj.org-article:1f5af1fef3a44d8a8f236de5a2388f042021-12-05T12:04:28ZAmino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis10.1038/s41419-021-04417-w2041-4889https://doaj.org/article/1f5af1fef3a44d8a8f236de5a2388f042021-12-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04417-whttps://doaj.org/toc/2041-4889Abstract 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 is unclear how these sensors are associated with cancer cell survival under low amino acid availability. In the present study, we investigated AKT activation in non-small cell lung cancer (NSCLC) cells deprived of each one of 20 amino acids. Among the 20 amino acids, deprivation of glutamine, arginine, methionine, and lysine induced AKT activation. AKT activation was induced by GCN2/ATF4/REDD1 axis-mediated mTORC2 activation under amino acid deprivation. In CRISPR-Cas9-mediated REDD1-knockout cells, AKT activation was not induced by amino acid deprivation, indicating that REDD1 plays a major role in AKT activation under amino acid deprivation. Knockout of REDD1 sensitized cells cultured under glutamine deprivation conditions to radiotherapy. Taken together, GCN2/ATF4/REDD1 axis induced by amino acid deprivation promotes cell survival signal, which might be a potential target for cancer therapy.Hyeon-Ok JinSung-Eun HongJi-Young KimSe-Kyeong JangIn-Chul ParkNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Hyeon-Ok Jin Sung-Eun Hong Ji-Young Kim Se-Kyeong Jang In-Chul Park Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis
description	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 is unclear how these sensors are associated with cancer cell survival under low amino acid availability. In the present study, we investigated AKT activation in non-small cell lung cancer (NSCLC) cells deprived of each one of 20 amino acids. Among the 20 amino acids, deprivation of glutamine, arginine, methionine, and lysine induced AKT activation. AKT activation was induced by GCN2/ATF4/REDD1 axis-mediated mTORC2 activation under amino acid deprivation. In CRISPR-Cas9-mediated REDD1-knockout cells, AKT activation was not induced by amino acid deprivation, indicating that REDD1 plays a major role in AKT activation under amino acid deprivation. Knockout of REDD1 sensitized cells cultured under glutamine deprivation conditions to radiotherapy. Taken together, GCN2/ATF4/REDD1 axis induced by amino acid deprivation promotes cell survival signal, which might be a potential target for cancer therapy.
format	article
author	Hyeon-Ok Jin Sung-Eun Hong Ji-Young Kim Se-Kyeong Jang In-Chul Park
author_facet	Hyeon-Ok Jin Sung-Eun Hong Ji-Young Kim Se-Kyeong Jang In-Chul Park
author_sort	Hyeon-Ok Jin
title	Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis
title_short	Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis
title_full	Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis
title_fullStr	Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis
title_full_unstemmed	Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis
title_sort	amino acid deprivation induces akt activation by inducing gcn2/atf4/redd1 axis
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/1f5af1fef3a44d8a8f236de5a2388f04
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Amino acid deprivation induces AKT activation by inducing GCN2/ATF4/REDD1 axis

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