The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation
Wang, Xuemin, Li, Wei, Parra, Josep-Lluis, Beugnet, Anne and Proud, Christopher G. (2003) The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation. Molecular and Cellular Biology, 23, (5), 1546-1557. (doi:10.1128/MCB.23.5.1546-1557.2003).
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Description/Abstract
Eukaryotic initiation factor 4E (eIF4E) binds the mRNA cap structure and forms eIF4F complexes that recruit 40S subunits to the mRNA. Formation of eIF4F is blocked by eIF4E-binding proteins such as 4E-BP1, which interacts with eIF4E via a motif in the center of its 118-residue sequence. 4E-BP1 plays key roles in cell proliferation, growth, and survival. Binding of 4E-BP1 to eIF4E is regulated by hierarchical multisite phosphorylation. Here we demonstrate that three different features in the C terminus of 4E-BP1 play distinct roles in regulating its phosphorylation and function. Firstly, we identify a new phosphorylation site in its C terminus (S101). A serine or glutamate at this position is required for efficient phosphorylation at Ser65. A second C-terminal site, S112, directly affects binding of 4E-BP1 to eIF4E without influencing phosphorylation of other sites. Thirdly, a conserved C-terminal motif influences phosphorylation of multiple residues, including rapamycin-insensitive sites. These relatively long-range effects are surprising given the reportedly unstructured nature of 4E-BP1 and may imply that phosphorylation of 4E-BP1 and/or binding to eIF4E induces a more-ordered structure. 4E-BP2 and -3 lack phosphorylatable residues corresponding to both S101 and S112. However, in 4E-BP3, replacement of the alanine at the position corresponding to S112 by serine or glutamate did not confer the ability to be released from eIF4E in response to insulin.
| Item Type: | Article |
|---|---|
| ISSNs: | 0270-7306 (print) |
| Related URLs: | |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Biological Sciences |
| Item ID: | 56211 |
| Date Deposited: | 07 Aug 2008 |
| Last Modified: | 12 May 2013 01:12 |
| Contributors: | Wang, Xuemin (Author) Li, Wei (Author) Parra, Josep-Lluis (Author) Beugnet, Anne (Author) Proud, Christopher G. (Author) |
| Date: | March 2003 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/56211 |
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