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Titolo:
THE HIGHLY ACIDIC C-TERMINAL REGION OF THE YEAST INITIATION-FACTOR SUBUNIT 2-ALPHA (EIF-2-ALPHA) CONTAINS CASEIN KINASE PHOSPHORYLATION SITES AND IS ESSENTIAL FOR MAINTAINING NORMAL REGULATION OF GCN4
Autore:
VANDENHEUVEL J; LANG V; RICHTER G; PRICE N; PEACOCK L; PROUD C; MCCARTHY JEG;
Indirizzi:
GBF,NATL BIOTECHNOL RES CTR,DEPT GENE EXPRESS,MASCHERODER WEG 1 D-38124 BRAUNSCHWEIG GERMANY GBF,NATL BIOTECHNOL RES CTR,DEPT GENE EXPRESS D-38124 BRAUNSCHWEIG GERMANY UNIV BRISTOL,SCH MED SCI,DEPT BIOCHEM BRISTOL BS8 1TD AVON ENGLAND
Titolo Testata:
Biochimica et biophysica acta, N. Gene structure and expression
fascicolo: 3, volume: 1261, anno: 1995,
pagine: 337 - 348
SICI:
0167-4781(1995)1261:3<337:THACRO>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-SYNTHESIS INITIATION; OLIGONUCLEOTIDE-DIRECTED MUTAGENESIS; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; ALPHA-SUBUNIT; FACTOR-II; TRANSLATIONAL INITIATION; RABBIT RETICULOCYTES; FACTOR-2-ALPHA; INHIBITION;
Keywords:
INITIATION FACTOR 2-ALPHA; PHOSPHORYLATION SITE; CASEIN KINASE; RECOMBINANT INITIATION FACTOR 2-ALPHA; (YEAST);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
J. Vandenheuvel et al., "THE HIGHLY ACIDIC C-TERMINAL REGION OF THE YEAST INITIATION-FACTOR SUBUNIT 2-ALPHA (EIF-2-ALPHA) CONTAINS CASEIN KINASE PHOSPHORYLATION SITES AND IS ESSENTIAL FOR MAINTAINING NORMAL REGULATION OF GCN4", Biochimica et biophysica acta, N. Gene structure and expression, 1261(3), 1995, pp. 337-348

Abstract

Regulation of the effective activity of eukaryotic initiation factor 2 (eIF-2) in protein synthesis is known to involve phosphorylation of its alpha subunit. Two mammalian enzymes, the haem-controlled repressor (HCR) and the double-stranded RNA-activated inhibitor (dsI), phosphorylate Ser-51 of the alpha subunit, thereby inhibiting the exchange ofbound nucleotides on, and thus the recycling of, eIF-2. In Saccharomyces cerevisiae, the equivalent serine seems to be phosphorylated by the GCN2 protein kinase, which is activated by amino acid starvation. However, in the present paper we show that this is not the only site of phosphorylation in yeast eIF-2 alpha. We report the preparation of recombinant yeast eIF-2 alpha from Escherichia coli and its use in in vitro phosphorylation studies. Mammalian HCR and dsI are shown to phosphorylate specifically Ser-51 of yeast eIF-alpha, whereas extracts from yeast cells do not. Instead, at least one of three serine residues in the acidic C-terminal region of this protein is phosphorylated by fractions of yeast possessing casein kinase activities 1 and 2. A triple Ser --> Ala mutant form of yeast eIF-2 alpha was found to be no longer phosphorylated by either of the yeast (or mammalian) casein kinase activities in vitro. Isoelectric focusing of yeast extracts confirmed thatthe mutated sites normally act as sites of phosphorylation in vivo. The same mutant was used to show that the three sites have no essentialfunction under normal physiological conditions in yeast. In contrast,deletion of the 13 amino acid long C-terminal region of eIF-2 alpha, including the three phosphorylation sites, led to derepression of GCN4in vivo. Thus removal of the short, highly acidic C-terminal region of eIF-2 alpha has the same regulatory effect on translational (re)initiation as phosphorylation of the Ser-51 residue of the wild-type protein. This result provides new insight into the role of eIF-2 alpha activity in the regulation of translational (re-) initiation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 05:38:03