The Ca 2+ -binding protein sorcin stimulates transcriptional activity of the unfolded protein response mediator ATF6

FEBS Letters

article

Steven Z. Parks¹  Tian Gao¹  Natalia Jimenez Awuapura¹  Joseph Ayathamattam¹  Pauline L. Chabosseau¹  Dhananjaya V. Kalvakolanu²  Héctor H. Valdivia³  Guy A. Rutter¹  Isabelle Leclerc¹ 

[1] Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion & Reproduction, Imperial College London;Departments of Microbiology and Immunology, University of Maryland School of Medicine;Cardiovascular Research Center, University of Wisconsin-Madison

关键词: ATF6;    ER stress;    lipotoxicity;    sorcin;   

DOI  :  10.1002/1873-3468.14101

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown