A Unique ISR Program Determines Cellular Responses to Chronic Stress

Guan, B.J.; van Hoef, V.; Jobava, R.; Elroy-Stein, O.; Valášek, Leoš Shivaya; Cargnello, M.; Gao, X.H.; Krokowski, D.; Merrick, W.C.; Kimball, S.R.; Komar, A.A.; Koromilas, A.E.; Wynshaw-Boris, A.; Topisirovic, I.; Larsson, O.; Hatzoglou, M.

doi:https://dx.doi.org/10.1016/j.molcel.2017.11.007

Number of the records: 1

A Unique ISR Program Determines Cellular Responses to Chronic Stress

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SYSNO ASEP	0483711
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	A Unique ISR Program Determines Cellular Responses to Chronic Stress
Author(s)	Guan, B.J. (US) van Hoef, V. (SE) Jobava, R. (US) Elroy-Stein, O. (IL) Valášek, Leoš Shivaya (MBU-M)_{RID, ORCID} Cargnello, M. (CA) Gao, X.H. (US) Krokowski, D. (US) Merrick, W.C. (US) Kimball, S.R. (US) Komar, A.A. (US) Koromilas, A.E. (CA) Wynshaw-Boris, A. (US) Topisirovic, I. (CA) Larsson, O. (SE) Hatzoglou, M. (US)
Source Title	Molecular Cell. - : Cell Press - ISSN 1097-2765 Roč. 68, č. 5 (2017), s. 885-900
Number of pages	6 s.
Language	eng - English
Country	US - United States
Keywords	UNFOLDED PROTEIN RESPONSE ; EUKARYOTIC TRANSLATION INITIATION ; ENDOPLASMIC-RETICULUM STRESS
Subject RIV	EE - Microbiology, Virology
OECD category	Microbiology
R&D Projects	GA17-06238S GA ČR - Czech Science Foundation (CSF)
Institutional support	MBU-M - RVO:61388971
UT WOS	000417646500009
EID SCOPUS	85037833477
DOI	10.1016/j.molcel.2017.11.007
Annotation	The integrated stress response (ISR) is a homeostatic mechanisminduced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis. The program includes PERK-dependent switching to an eIF3-dependent translation initiation mechanism, resulting in partial, but not complete, translational recovery, which, together with transcriptional reprogramming, selectively bolsters expression of proteins with ER functions. Coordination of transcriptional and translational reprogramming prevents ER dysfunction and inhibits 'foamy cell' development, thus establishing a molecular basis for understanding human diseases associated with ER dysfunction.
Workplace	Institute of Microbiology
Contact	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Year of Publishing	2018

Number of the records: 1