| First Author | Scheuner D | Year | 2001 |
| Journal | Mol Cell | Volume | 7 |
| Issue | 6 | Pages | 1165-76 |
| PubMed ID | 11430820 | Mgi Jnum | J:70004 |
| Mgi Id | MGI:2136066 | Doi | 10.1016/s1097-2765(01)00265-9 |
| Citation | Scheuner D, et al. (2001) Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell 7(6):1165-76 |
| abstractText | 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. |
