An integrated stress response regulates amino acid metabolism and resistance to oxidative stress

被引：2680

作者：

Harding, HP

Zhang, YH

Zeng, HQ

Novoa, I

Lu, PD

Calfon, M

Sadri, N

Yun, C

Popko, B

Paules, R

Stojdl, DF

Bell, JC

Hettmann, T

Leiden, JM

Ron, D ^{[1
]}

机构：

[1] NYU, Sch Med, Skirball Inst, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA

[3] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA

[4] NIEHS, Res Triangle Pk, NC 27709 USA

[5] Ottawa Reg Canc Ctr, Ottawa, ON K1H 8L6, Canada

[6] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA

来源：

MOLECULAR CELL | 2003年 / 11卷 / 03期

关键词：

D O I：

10.1016/S1097-2765(03)00105-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Eukaryotic cells respond to unfolded proteins in their endoplasmic reticulum (ER stress), amino acid starvation, or oxidants by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha). This adaptation inhibits general protein synthesis while promoting translation and expression of the transcription factor ATF4. Atf4(-/-) cells are impaired in expressing genes involved in amino acid import, glutathione biosynthesis, and resistance to oxidative stress. Perk(-/-) cells, lacking an upstream ER stress-activated eIF2alpha kinase that activates Atf4, accumulate endogenous peroxides during ER stress, whereas interference with the ER oxidase ERO1 abrogates such accumulation. A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress.

引用

页码：619 / 633

页数：15

共 59 条

[1] Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene [J].