A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress

Shutoff of global protein synthesis is a conserved response to cellular stresses. This general phenomenon is accompanied by the induction of distinct gene programs tailored to each stress. Although the mechanisms driving repression of general protein synthesis are well characterized, how cells repro...

Full description

Saved in:
Bibliographic Details
Published inScience (American Association for the Advancement of Science) Vol. 370; no. 6518; pp. 853 - 856
Main Authors Lamper, Adam M, Fleming, Rebecca H, Ladd, Kayla M, Lee, Amy S Y
Format Journal Article
LanguageEnglish
Published United States The American Association for the Advancement of Science 13.11.2020
Subjects
Adaptation
Adaptation, Physiological
Cap-binding protein
Cell activation
Cell Survival
Cellular stress response
Deprivation
Environmental regulations
Environmental stress
Eukaryotic Initiation Factor-3 - biosynthesis
Eukaryotic Initiation Factor-3 - genetics
Gene expression
Glucose
Glucose - deficiency
HEK293 Cells
Homeostasis
Humans
Mammalian cells
Mammals
Metabolism
Phosphorylation
Protein Biosynthesis
Protein synthesis
Proteins
Rapamycin
Starvation
Stress, Physiological
Stresses
Survival
TOR protein
TOR Serine-Threonine Kinases - metabolism
Translation
Online AccessGet full text

Cover

More Information
Summary:Shutoff of global protein synthesis is a conserved response to cellular stresses. This general phenomenon is accompanied by the induction of distinct gene programs tailored to each stress. Although the mechanisms driving repression of general protein synthesis are well characterized, how cells reprogram the translation machinery for selective gene expression remains poorly understood. Here, we found that the noncanonical 5' cap-binding protein eIF3d was activated in response to metabolic stress in human cells. Activation required reduced CK2-mediated phosphorylation near the eIF3d cap-binding pocket. eIF3d controls a gene program enriched in factors important for glucose homeostasis, including members of the mammalian target of rapamycin (mTOR) pathway. eIF3d-directed translation adaptation was essential for cell survival during chronic glucose deprivation. Thus, this mechanism of translation reprogramming regulates the cellular response to metabolic stress.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abb0993