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

FEBS Letters

Blenis, John¹  Tee, Andrew R¹  Tee, Jennifer A¹ 

[1] Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA

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;    eIF4E;    eukaryotic initiation factor 4E;    4E-BP1;    eukaryotic initiation factor 4E-binding protein 1;    4EHP;    eIF4E homologous protein;    HEK293E;    human embryonic kidney 293E;    S6K1;    ribosomal protein S6 kinase 1;    m7GTP;    7-methylguanosine triphosphate;   

DOI  :  10.1016/S0014-5793(04)00313-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown