Two distinct nodes of translational inhibition in the Integrated Stress Response.

Abstract:

:The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated eIF2α kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor eIF2α. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes. [BMB Reports 2017; 50(11): 539-545].

journal_name

BMB Rep

journal_title

BMB reports

authors

Ryoo HD,Vasudevan D

doi

10.5483/bmbrep.2017.50.11.157

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

539-545

issue

11

eissn

1976-6696

issn

1976-670X

pii

3957

journal_volume

50

pub_type

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