Characterizing the interaction of the mammalian eIF4E‐related protein 4EHP with 4E‐BP1
- 9 April 2004
- journal article
- Published by Wiley in FEBS Letters
- Vol. 564 (1-2) , 58-62
- https://doi.org/10.1016/s0014-5793(04)00313-8
Abstract
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.Keywords
This publication has 13 references indexed in Scilit:
- Inactivation of the Tuberous Sclerosis Complex-1 and -2 Gene Products Occurs by Phosphoinositide 3-Kinase/Akt-dependent and -independent Phosphorylation of TuberinJournal of Biological Chemistry, 2003
- TOS Motif-Mediated Raptor Binding Regulates 4E-BP1 Multisite Phosphorylation and FunctionCurrent Biology, 2003
- The C Terminus of Initiation Factor 4E-Binding Protein 1 Contains Multiple Regulatory Features That Influence Its Function and PhosphorylationMolecular and Cellular Biology, 2003
- Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4EGenes & Development, 2002
- Identification of a Conserved Motif Required for mTOR SignalingPublished by Elsevier ,2002
- Regulation of translation initiation by FRAP/mTORGenes & Development, 2001
- Regulation of Ribosomal S6 Kinase 2 by Effectors of the Phosphoinositide 3-Kinase PathwayPublished by Elsevier ,2001
- Repressor binding to a dorsal regulatory site traps human eIF4E in a high cap-affinity stateThe EMBO Journal, 1999
- Cooperative modulation by eIF4G of eIF4E-binding to the mRNA 5' cap in yeast involves a site partially shared by p20The EMBO Journal, 1998
- Mammalian Ras interacts directly with the serine/threonine kinase rafPublished by Elsevier ,1993