eIF4E/4E-BP dissociation and 4E-BP degradation in the first mitotic division of the sea urchin embryo.
The mRNA's cap-binding protein eukaryotic translation initiation factor (eIF)4E is a major target for the regulation of translation initiation. eIF4E activity is controlled by a family of translation inhibitors, the eIF4E-binding proteins (4E-BPs). We have previously shown that a rapid dissociation of 4E-BP from eIF4E is related with the dramatic rise in protein synthesis that occurs following sea urchin fertilization. Here, we demonstrate that 4E-BP is destroyed shortly following fertilization and that 4E-BP degradation is sensitive to rapamycin, suggesting that proteolysis could be a novel means of regulating 4E-BP function. We also show that eIF4E/4E-BP dissociation following fertilization is sensitive to rapamycin. Furthermore, while rapamycin modestly affects global translation rates, the drug strongly inhibits cyclin B de novo synthesis and, consequently, precludes the completion of the first mitotic cleavage. These results demonstrate that, following sea urchin fertilization, cyclin B translation, and thus the onset of mitosis, are regulated by a rapamycin-sensitive pathway. These processes are effected at least in part through eIF4E/4E-BP complex dissociation and 4E-BP degradation.
Salaün
Patrick
P
Station Biologique de Roscoff, Université Pierre et Marie Curie (EI 37), Centre National dela Recherche Scientifique (CNRS, UMR 7127), Institut National des Sciences de l'Univers (INSU), B.P. 74, 29682, Roscoff Cedex, France.
Pyronnet
Stéphane
S
Morales
Julia
J
Mulner-Lorillon
Odile
O
Bellé
Robert
R
Sonenberg
Nahum
N
Cormier
Patrick
P
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D005306:Fertilization / Q000502:physiology; D008297:Male; D008938:Mitosis / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism*; D012617:Sea Urchins / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology
D002352:Carrier Proteins; D019926:Cyclin B; D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins; D016203:CDC2 Protein Kinase; D020123:Sirolimus