The eIF4E repressor protein 4E-BP2 is merely truncated, despite 4E-BP1 degradation in the porcine uterine tissue during implantation

被引:4
作者
Wollenhaupt, Karin [1 ]
Bruessow, Klaus-Peter [1 ]
Albrecht, Dirk [2 ]
Tomek, Wolfgang [1 ]
机构
[1] Leibniz Inst Farm Anim Biol, D-18196 Dummerstorf, Germany
[2] Ernst Moritz Arndt Univ Greifswald, Inst Microbiol, Greifswald, Germany
关键词
CAP-BINDING PROTEIN; IN-VITRO MATURATION; INITIATION-FACTOR; 4E; TRANSLATION INITIATION; DEPENDENT TRANSLATION; DIFFERENTIAL REGULATION; 4E-BINDING PROTEIN-1; GENE-EXPRESSION; BOVINE OOCYTES; MICE LACKING;
D O I
10.1002/mrd.22108
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
Recently, we identified an N-terminally truncated form of the mRNA cap binding protein eIF4E in the porcine luminal epithelium during implantation. EIF4E truncation is accompanied by degradation of the eIF4E-repressor protein 4E-BP1. In this study, we investigated whether or not the other members of the eIF4E-repressor family, namely 4E-BP2 and 4E-BP3, were also modified during early pregnancy. We did not detect 4E-BP3 in the uterine tissue; however, 4E-BP2 emerged in one or two stable fragments on pregnancy day 15. 4E-BP2 truncation most likely occurs at the N-terminus, and this calcium-stimulated processing depends on progesterone and estradiol. The activities targeting eIF4E, 4E-BP1, and 4E-BP2 were found in different fractions after anionic exchange chromatography, indicating the action of different proteases. Detailed protein interaction studies with immobilized anti-eIF4E and m7GTP-Sepharose showed a differential binding of the 4E-BP2 isoforms to the eIF4E variants and to the cap structure. In general, truncation of eIF4E reduces the inhibitory impact of 4E-BP2, whereas truncation of 4E-BP2 restores repression by binding the prototype eIF4E. In this context, we suggest long-term translational repression by the truncated 4E-BP2 is affected by the loss of the RAIP motif located at the N-terminus, which is indispensable for phosphorylation and deactivation of the molecule. In conclusion, we propose a tightly balanced regulation of the truncation of the cap-binding complex component eIF4F and degradation of 4E-BP1 and/or truncation of 4E-BP2 that together ensures correct translational control during the dynamic process of conceptus implantation. Mol. Reprod. Dev. 79: 767776, 2012. (C) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:767 / 776
页数:10
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