Synthetic embryonic lethality upon deletion of the ER cochaperone p58IPK and the ER stress sensor ATF6α

Javier A Gomez; Heather M Tyra; Diane DeZwaan-McCabe; Alicia K Olivier; D. Thomas Rutkowski

doi:10.1016/j.bbrc.2013.11.060

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Synthetic embryonic lethality upon deletion of the ER cochaperone p58IPK and the ER stress sensor ATF6α

Journal article

Peer reviewed

Synthetic embryonic lethality upon deletion of the ER cochaperone p58IPK and the ER stress sensor ATF6α

Javier A Gomez, Heather M Tyra, Diane DeZwaan-McCabe, Alicia K Olivier and D. Thomas Rutkowski

Biochemical and biophysical research communications, Vol.443(1), pp.115-119

01/03/2014

DOI: 10.1016/j.bbrc.2013.11.060

PMCID: PMC3901050

PMID: 24275136

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Abstract

•The ER stress sensing molecule ATF6α is dispensable for normal tissue organization.•Heterozygosity for p58IPK does not sensitize Atf6α−/− animals to hepatic ER stress.•Combined homozygous deletion of ATF6α and the ER cochaperone p58IPK leads to embryonic lethality.•An intact UPR can compensate for genetic disruption of ER protein folding in vivo. The unfolded protein response (UPR) is activated as a consequence of alterations to ER homeostasis. It upregulates a group of ER chaperones and cochaperones, as well as other genes that improve protein processing within the secretory pathway. The UPR effector ATF6α augments—but is not essential for—maximal induction of ER chaperones during stress, yet its role, if any, in protecting cellular function during normal development and physiology is unknown. A systematic analysis of multiple tissues from Atf6α−/− mice revealed that all tissues examined were grossly insensitive to loss of ATF6α. However, combined deletion of ATF6α and the ER cochaperone p58IPK resulted in synthetic embryonic lethality. These findings reveal for the first time that an intact UPR can compensate for the genetic impairment of protein folding in the ER in vivo. The also expose a role for p58IPK in normal embryonic development.

Protein Folding

ER stress

Chaperones

Unfolded protein response

Details

Title: Subtitle: Synthetic embryonic lethality upon deletion of the ER cochaperone p58IPK and the ER stress sensor ATF6α
Creators: Javier A Gomez - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Heather M Tyra - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Diane DeZwaan-McCabe - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Alicia K Olivier - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
D. Thomas Rutkowski - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.443(1), pp.115-119
DOI: 10.1016/j.bbrc.2013.11.060
PMID: 24275136
PMCID: PMC3901050
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: Elsevier BV
Grant note: DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney, award: R01 DK084058
Language: English
Date published: 01/03/2014
Academic Unit: Anatomy and Cell Biology; Internal Medicine
Record Identifier: 9984094328602771

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