Jagn1 Is Induced in Response to ER Stress and Regulates Proinsulin Biosynthesis

PloS One
Courtney NosakAllen Volchuk

Abstract

The Jagn1 protein was indentified in a SILAC proteomic screen of proteins that are increased in insulinoma cells expressing a folding-deficient proinsulin. Jagn1 mRNA was detected in primary rodent islets and in insulinoma cell lines and the levels were increased in response to ER stress. The function of Jagn1 was assessed in insulinoma cells by both knock-down and overexpression approaches. Knock-down of Jagn1 caused an increase in glucose-stimulated insulin secretion resulting from an increase in proinsulin biosynthesis. In contrast, overexpression of Jagn1 in insulinoma cells resulted in reduced cellular proinsulin and insulin levels. Our results identify a novel role for Jagn1 in regulating proinsulin biosynthesis in pancreatic β-cells. Under ER stress conditions Jagn1 is induced which might contribute to reducing proinsulin biosynthesis, in part by helping to relieve the protein folding load in the ER in an effort to restore ER homeostasis.

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Citations

Jul 26, 2018·Journal of Pediatric Hematology/oncology·Cristina CifaldiAndrea Finocchi
Feb 7, 2020·Journal of Assisted Reproduction and Genetics·T PiniM Katz-Jaffe

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Methods Mentioned

BETA
protein folding
reverse transcription PCR
PCR
transfection
protein assay
glycosylation
immunoprecipitation
confocal microscopy
Two-Hybrid

Software Mentioned

ImageQuant
SILAC
WebGestalt

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