EIF2S1

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EIF2S1
Protein EIF2S1 PDB 1kl9.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases EIF2S1, EIF-2, EIF-2A, EIF-2alpha, EIF2, EIF2A, eukaryotic translation initiation factor 2 subunit alpha
External IDs MGI: 95299 HomoloGene: 3020 GeneCards: EIF2S1
RNA expression pattern
PBB GE EIF2S1 201144 s at fs.png

PBB GE EIF2S1 201143 s at fs.png

PBB GE EIF2S1 201142 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004094

NM_026114

RefSeq (protein)

NP_004085

NP_080390.1
NP_080390

Location (UCSC) Chr 14: 67.36 – 67.39 Mb Chr 12: 78.86 – 78.89 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the EIF2S1 gene.[3][4]

Function[edit]

The protein encoded by this gene is the alpha (α) subunit of the translation initiation factor eIF2 complex which catalyzes an early regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA (Met-tRNAiMet) to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (α, 36 kD, this article), beta (β, 38 kD), and gamma (γ, 52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation state of eIF2α.[4]

Clinical significance[edit]

After reperfusion following brain ischemia, there is inhibition of neuron protein synthesis due to phosphorylation of eIF2α. There is colocalization between phosphorylated eIF2α and cytosolic cytochrome c, which is released from mitochondria in apoptosis. Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of eIF2α triggers cytochrome c release during apoptotic cell death.[5]

Mice heterozygous for the S51A mutation become obese and diabetic on a high-fat diet. Glucose intolerance resulted from reduced insulin secretion, defective transport of proinsulin, and a reduced number of insulin granules in beta cells. Hence proper functioning of eIF2α appears essential for preventing diet-induced type II diabetes.[6]

Dephosphorylation inhibitors[edit]

Salubrinal is a selective inhibitor of enzymes that dephosphorylate eIF2α.[7] Salubrinal also blocks eIF2α dephosphorylation by a herpes simplex virus protein and inhibits viral replication. eIF2α phosphorylation is cytoprotective during endoplasmic reticulum stress.[8][9]

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Ernst H, Duncan RF, Hershey JW (Mar 1987). "Cloning and sequencing of complementary DNAs encoding the alpha-subunit of translational initiation factor eIF-2. Characterization of the protein and its messenger RNA". J Biol Chem. 262 (3): 1206–12. PMID 2948954. 
  4. ^ a b "Entrez Gene: EIF2S1 eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa". National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2010-10-05. 
  5. ^ Page AB, Owen CR, Kumar R, Miller JM, Rafols JA, White BC, DeGracia DJ, Krause GS (July 2003). "Persistent eIF2alpha(P) is colocalized with cytoplasmic cytochrome c in vulnerable hippocampal neurons after 4 hours of reperfusion following 10-minute complete brain ischemia". Acta Neuropathol. 106 (1): 8–16. doi:10.1007/s00401-003-0693-2. PMID 12687390. 
  6. ^ Scheuner D, Vander Mierde D, Song B, Flamez D, Creemers JW, Tsukamoto K, Ribick M, Schuit FC, Kaufman RJ (July 2005). "Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis". Nat. Med. 11 (7): 757–764. doi:10.1038/nm1259. PMID 15980866. 
  7. ^ Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J (February 2005). "A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress". Science. 307 (5711): 935–939. doi:10.1126/science.1101902. PMID 15705855. 
  8. ^ Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D (May 2000). "Perk is essential for translational regulation and cell survival during the unfolded protein response". Mol. Cell. 5 (5): 897–904. doi:10.1016/S1097-2765(00)80330-5. PMID 10882126. 
  9. ^ Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, Saunders T, Bonner-Weir S, Kaufman RJ (June 2001). "Translational control is required for the unfolded protein response and in vivo glucose homeostasis". Mol. Cell. 7 (6): 1165–1176. doi:10.1016/S1097-2765(01)00265-9. PMID 11430820. 

Further reading[edit]