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The Ca 2+ ‐binding protein sorcin stimulates transcriptional activity of the unfolded protein response mediator ATF6
Author(s) -
Parks Steven Z.,
Gao Tian,
Jimenez Awuapura Natalia,
Ayathamattam Joseph,
Chabosseau Pauline L.,
Kalvakolanu Dhananjaya V.,
Valdivia Héctor H.,
Rutter Guy A.,
Leclerc Isabelle
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14101
Subject(s) - atf6 , unfolded protein response , endoplasmic reticulum , downregulation and upregulation , mediator , chemistry , microbiology and biotechnology , transcription factor , activating transcription factor , medicine , endocrinology , biology , biochemistry , gene
Sorcin is a calcium‐binding protein involved in maintaining endoplasmic reticulum (ER) Ca 2+ 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.