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Titolo:
A quantitative molecular model for modulation of mammalian translation by the eIF4E-binding protein 1
Autore:
Karim, MM; Hughes, JMX; Warwicker, J; Scheper, GC; Proud, CG; McCarthy, JEG;
Indirizzi:
UMIST, Dept Biomol Sci, Posttranscript Control Grp, Manchester M60 1QD, Lancs, England UMIST Manchester Lancs England M60 1QD Manchester M60 1QD, Lancs, England Univ Dundee, Sch Life Sci, Dundee DD1 5EH, Scotland Univ Dundee Dundee Scotland DD1 5EH h Life Sci, Dundee DD1 5EH, Scotland
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 23, volume: 276, anno: 2001,
pagine: 20750 - 20757
SICI:
0021-9258(20010608)276:23<20750:AQMMFM>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
INITIATION-FACTOR EIF-4E; MESSENGER-RNA 5'-CAP; FACTOR 4G EIF4G; SACCHAROMYCES-CEREVISIAE; DEPENDENT TRANSLATION; IN-VIVO; PHAS-I; PHOSPHORYLATION SITES; ESCHERICHIA-COLI; CAP-AFFINITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: McCarthy, JEG UMIST, Dept Biomol Sci, Posttranscript Control Grp, POB 88, Manchester M601QD, Lancs, England UMIST POB 88 Manchester Lancs England M601QD Lancs, England
Citazione:
M.M. Karim et al., "A quantitative molecular model for modulation of mammalian translation by the eIF4E-binding protein 1", J BIOL CHEM, 276(23), 2001, pp. 20750-20757

Abstract

Translation initiation is a key point of regulation in eukaryotic gene expression. 4E-binding proteins (4E-BPs) inhibit initiation by blocking the association of eIF4E with eIF4G, two integral components of the mRNA cap-binding complex. Phosphorylation of 4E-BP1 reduces its ability to bind to eIF4Eand thereby to compete with eIF4G. A novel combination of biophysical and biochemical tools was used to measure the impact, of phosphorylation and acidic side chain substitution at each potentially modulatory site in 4E-BP1. For each individual site, we have analyzed the effects of modification on eIF4E binding using affinity chromatography and surface plasmon resonance analysis, and on the regulatory function of the 4E-BP1 protein using a yeastin vivo model system and a mammalian in vitro translation assay. We find that modifications at the two sites immediately flanking the eIF4E-binding domain, Thr(46) and Ser(65), consistently have the most significant effects,and that phosphorylation of Ser(65) causes the greatest reduction in binding affinity. These results establish a quantitative framework that should contribute to understanding of the molecular interactions underlying 4E-BP1-mediated translational regulation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 09:49:19