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Insulin modulates induction of glucose‐regulated protein 78 during endoplasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells
Author(s) -
Inageda Kiyoshi
Publication year - 2010
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 - 10.1016/j.febslet.2010.07.040
Subject(s) - endoplasmic reticulum , atf4 , unfolded protein response , microbiology and biotechnology , chemistry , protein expression , neuroblastoma , endocrinology , medicine , glucose regulated protein , biology , biochemistry , cell culture , gene , genetics
The effect of insulin on endoplasmic reticulum (ER) stress was investigated. Insulin protected cell death induced by ER stress and increased glucose‐regulated protein 78 (GRP78) mRNA and protein levels. Insulin also significantly increased activating transcription factor‐4 (ATF4) protein in the nucleus, which was inhibited by LY294002, a phosphatidylinositol 3‐kinase (PI‐3 kinase) inhibitor. The increase of ATF4 protein by insulin was not due to transcriptional or translational up‐regulation but to a post‐translational mechanism. Knockdown of ATF4 by siRNA significantly inhibited GRP78 induction by insulin. These results indicate that insulin modulated ER stress‐induced GRP78 expression occurs via ATF4 up‐regulation.