Characterizing the interaction of the mammalian eIF4E-related protein 4EHP with 4E-BP1

被引：22

作者：

Tee, AR ^{[1
]}

Tee, JA ^{[1
]}

Blenis, J ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

来源：

FEBS LETTERS | 2004年 / 564卷 / 1-2期

关键词：

eukaryotic initiation factor 4E-binding protein 1; eukaryotic initiation factor 4E homologous protein; eukaryotic initiation factor 4E; translation; initiation factor; 7-methylguanosine triphosphate;

D O I：

10.1016/S0014-5793(04)00313-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) represses translation initiation by binding to eukaryotic initiation factor 4E (eIF4E). 4E-BP1 also binds to the eIF4E homologous protein (4EHP). We show that eIF4E-binding mutants of 4E-BP1 (Y54A and L59A) fail to form heterodimeric complexes with wild-type 4EHP. In addition, the W95A mutant of 4EHP, similar to a homologous mutation in eIF4E, inhibits its binding to wild-type 4E-BP1. Interestingly, 4EHP over-expression instigates a negative feedback loop that inhibits upstream signaling to 4E-BP1 and ribosomal protein S6 kinase 1 (S6K1) whereas the 4E-BP1-binding-deficient mutant of 4EHP(W95A) was unable to trigger this feedback loop. Thus, the interaction of 4EHP with 4E-BP1 is necessary for this observed impaired signaling to 4E-BP1 and S6K1. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：58 / 62

页数：5

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