Translational control is required for the unfolded protein response and in vivo glucose homeostasis
| Autor: | Chuan Liu, Donalyn Scheuner, Thom Saunders, Susan Bonner-Weir, Benbo Song, Randal J. Kaufman, Edward L. McEwen, Patrick J. Gillespie, Ross Laybutt |
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| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
Protein Folding Cell Survival Gene Expression Biology Endoplasmic Reticulum environment and public health Islets of Langerhans Mice Eukaryotic translation Translational regulation Glucose homeostasis Initiation factor Animals Homeostasis EIF2AK3 RNA Messenger Phosphorylation Molecular Biology Endoplasmic Reticulum Chaperone BiP Germ-Line Mutation Heat-Shock Proteins Endoplasmic reticulum Homozygote Gluconeogenesis Cell Biology Blood Proteins Molecular biology Activating Transcription Factors Hypoglycemia Mice Mutant Strains DNA-Binding Proteins enzymes and coenzymes (carbohydrates) Glucose Animals Newborn Mutagenesis Protein Biosynthesis Unfolded protein response CCAAT-Enhancer-Binding Proteins Carrier Proteins Transcription Factor CHOP Molecular Chaperones Transcription Factors |
| Zdroj: | Molecular cell. 7(6) |
| ISSN: | 1097-2765 |
| Popis: | The accumulation of unfolded protein in the endoplasmic reticulum (ER) attenuates protein synthesis initiation through phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) at Ser51. Subsequently, transcription of genes encoding adaptive functions including the glucose-regulated proteins is induced. We show that eIF2alpha phosphorylation is required for translation attenuation, transcriptional induction, and survival in response to ER stress. Mice with a homozygous mutation at the eIF2alpha phosphorylation site (Ser51Ala) died within 18 hr after birth due to hypoglycemia associated with defective gluconeogenesis. In addition, homozygous mutant embryos and neonates displayed a deficiency in pancreatic beta cells. The results demonstrate that regulation of translation through eIF2alpha phosphorylation is essential for the ER stress response and in vivo glucose homeostasis. |
| Databáze: | OpenAIRE |
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