Natural occurrence and physiological role of a truncated eIF4E in the porcine endometrium during implantation.
The present study is the first report providing evidence for a physiological role of a truncated form of the mRNA cap-binding protein eIF4E1 (eukaryotic initiation factor 4E1). Our initial observation was that eIF4E, which mediates the mRNA cap function by recruiting the eIF4F complex (composed of eIF4E, 4G and 4A), occurs in two forms in porcine endometrial tissue in a strictly temporally restricted fashion. The ubiquitous prototypical 25 kDa form of eIF4E was found in ovariectomized and cyclic animals. A new stable 23 kDa variant, however, is predominant during early pregnancy at the time of implantation. Northern blotting, cDNA sequence analysis, in vitro protease assays and MS showed that the 23 kDa form does not belong to a new class of eIF4E proteins. It represents a proteolytically processed variant of eIF4E1, lacking not more than 21 amino acids at the N-terminus. Steroid replacements indicated that progesterone in combination with 17β-oestradiol induced the formation of the 23 kDa eIF4E. Modified cell-free translation systems mimicking the situation in the endometrium revealed that, besides eIF4E, eIF4G was also truncated, but not eIF4A or PABP [poly(A)-binding protein]. The 23 kDa form of eIF4E reduced the repressive function of 4E-BP1 (eIF4E-binding protein 1) and the truncated eIF4G lacked the PABP-binding site. Thus we suggest that the truncated eIF4E provides an alternative regulation mechanism by an altered dynamic of eIF4E/4E-BP1 binding under conditions where 4E-BP1 is hypophosphorylated. Together with the impaired eIF4G-PABP interaction, the modified translational initiation might particularly regulate protein synthesis during conceptus attachment at the time of implantation.
Wollenhaupt
Karin
K
Department of Reproductive Biology, Leibniz Institute for Farm Animal Biology, Wilhelm-Stahl-Allee 2, D-18196 Dummerstorf, Germany.
Reinke
Kati
K
Brüssow
Klaus-Peter
KP
Albrecht
Dirk
D
Tiemann
Ute
U
Seyfert
Hans-Martin
HM
Tomek
Wolfgang
W
D000818:Animals; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology*; D004717:Endometrium / Q000502:physiology*; D004971:Estrus / Q000502:physiology; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics* / Q000378:metabolism; D005260:Female; D009928:Organ Specificity; D010060:Ovulation / Q000502:physiology; D011247:Pregnancy; D014176:Protein Biosynthesis; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D017384:Sequence Deletion; D013552:Swine
D039561:Eukaryotic Initiation Factor-4E