title: The eIF4E repressor protein 4E-BP2 is merely truncated, despite 4E-BP1 degradation in the porcine uterine tissue during implantation.
abstract: 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 m(7) GTP-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.
authors.affiliation: Leibniz Institute for Farm Animal Biology, Reproductive Biology, Dummerstorf, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Wollenhaupt
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Brüssow
authors.forename: Dirk
authors.initials: D
authors.lastname: Albrecht
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tomek
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium; D010064:Embryo Implantation / Q000502:physiology*; D004958:Estradiol; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D010766:Phosphorylation; D011247:Pregnancy; D011374:Progesterone; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013552:Swine; D014599:Uterus / Q000378:metabolism
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D020033:Protein Isoforms; D012097:Repressor Proteins; D011374:Progesterone; D004958:Estradiol; D002118:Calcium