The Ca2+ -binding protein sorcin stimulates transcriptional activity of the unfolded protein response mediator ATF6.

Steven Z Parks, Tian Gao, Natalia Jimenez Awuapura, Joseph Ayathamattam, Pauline L Chabosseau, Dhananjaya V Kalvakolanu, Héctor H Valdivia, Guy A Rutter, Isabelle Leclerc

FEBS letters 2021 Jul

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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. © 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Citation

Steven Z Parks, Tian Gao, Natalia Jimenez Awuapura, Joseph Ayathamattam, Pauline L Chabosseau, Dhananjaya V Kalvakolanu, Héctor H Valdivia, Guy A Rutter, Isabelle Leclerc. The Ca2+ -binding protein sorcin stimulates transcriptional activity of the unfolded protein response mediator ATF6. FEBS letters. 2021 Jul;595(13):1782-1796