The Ca2+-binding protein sorcin stimulates transcriptional activity of the unfolded protein response mediator ATF6
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Sorcin is a calcium-binding protein involved in maintaining endoplasmic reticulum (ER) Ca2+ stores. We have previously shown that overexpressing sorcin under the rat insulin promoter was protective against high-fat diet-induced pancreatic beta-cell dysfunction in vivo. Activating transcription factor 6 (ATF6) is a key mediator of the unfolded protein response (UPR) that provides cellular protection during the progression of ER stress. Here, using nonexcitable HEK293 cells, we show that sorcin overexpression increased ATF6 signalling, whereas sorcin knock out caused a reduction in ATF6 transcriptional activity and increased ER stress. Altogether, our data suggest that sorcin downregulation during lipotoxic stress may prevent full ATF6 activation and a normal UPR during the progression of obesity and insulin resistance.
Date Issued
2021-07
Date Acceptance
2021-04-21
Citation
FEBS Letters, 2021, 595 (13), pp.1782-1796
ISSN
0014-5793
Publisher
Elsevier
Start Page
1782
End Page
1796
Journal / Book Title
FEBS Letters
Volume
595
Issue
13
Copyright Statement
© 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Diabetes UK
MRC Programme Grant
Rosetrees Trust
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000653160600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
12/0004535
MR/R022259/1
M529
212625/Z/18/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biophysics
Cell Biology
ATF6
ER stress
lipotoxicity
sorcin
ENDOPLASMIC-RETICULUM STRESS
ER STRESS
INSULIN-RESISTANCE
CRYSTAL-STRUCTURE
CALCIUM-RELEASE
BINDING
MODULATION
ACTIVATION
PROTEOLYSIS
HOMEOSTASIS
Publication Status
Published
Date Publish Online
2021-05-07