title: 4E-BP1 degradation and eIF4E truncation occur spatially distinctly in the porcine uterine epithelia and are features of noninvasive implantation in the pig.
abstract: The implantation of the blastocyst into the endometrium is an indispensable premise for successful embryonic development. This process is regulated by maternal and embryonic signals that influence gene expression at the translational level, among other processes. Recently, we have shown that proteolytical cleavage of the prototypical 25-kDa, mRNA cap-binding protein eIF4E produces a stable variant with a molecular mass of approximately 23 kDa exclusively in the porcine endometrium during implantation. This is accompanied by dephosphorylation and reduction of the abundant repressor 4E-BP1. Here, we investigate the distribution of the truncated eIF4E and of 4E-BP1 in the porcine uterine tissue, their binding in native samples, and we analyzed eIF4E-, eIF4G-, and 4E-BP1-specific proteolytic activities. Our results show that in pigs, the truncated eIF4E is located in the endometrial luminal epithelium during implantation. Neither glandulary tissue nor stroma expressed any truncated eIF4E. The reduced abundance of 4E-BP1 during implantation is mainly the result of decay in the glandular epithelia. Moreover, steroid replacements, in vitro protease assays, and cell lysate fractionation showed that eIF4E cleavage and 4E-BP1 decay both depended on the ovarian steroid hormones estradiol and progestrone, but these effects are the result of different proteolytic activities. Although eIF4G cleavage also depends on calcium, stimulation by these steroids could not be established. We propose that the translation initiation process in the endometrium is differently regulated by the truncated eIF4E, utilizing different abundances of 4E-BP1 and binding dynamic of eIF4E/4E-BP1 in distinct forms of implantation.
authors: Leibniz Institute for Farm Animal Biology, Reproductive Biology, Dummerstorf, Germany.
authors: Karin
authors: K
authors: Wollenhaupt
authors: Kati
authors: K
authors: Reinke
authors: Klaus-Peter
authors: KP
authors: Brüssow
authors: Wilhelm
authors: W
authors: Kanitz
authors: Wolfgang
authors: W
authors: Tomek
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism*; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D006651:Histocytochemistry; D010447:Peptide Hydrolases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism*; D013552:Swine
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins; D012097:Repressor Proteins; D010447:Peptide Hydrolases; D002118:Calcium