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Provedor de dados:  5
País:  France
Título:  Modelization of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of elF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive
Autores:  Laurent, Sebastien
Richard, Adrien
Mulner-lorillon, Odile
Morales, Julia
Flament, Didier
Glippa, Virginie
Bourdon, Jeremie
Gosselin, Pauline
Siegel, Anne
Cormier, Patrick
Belle, Robert
Data:  2014-05
Ano:  2014
Palavras-chave:  Translational control
Sea urchin embryos
Mechanisms of fertilization
Deterministic model
Translation simulation
Resumo:  Fertilization of sea urchin eggs involves an increase in protein synthesis associated with a decrease in the amount of the translation initiation inhibitor 4E-BP A highly simple reaction model for the regulation of protein synthesis was built and was used to simulate the physiological changes in the total 4E-BP amount observed during time after fertilization. Our study evidenced that two changes occurring at fertilization are necessary to fit with experimental data. The first change was an 8-fold increase in the dissociation parameter (koffi) of the elF4E:4E-BP complex. The second was an important 32.5-fold activation of the degradation mechanism of the protein 4E-BP Additionally, the changes in both processes should occur in 5 min time interval post-fertilization. To validate the model, we checked that the kinetic of the predicted 4.2-fold increase of elF4E:e1F4G complex concentration at fertilization matched the increase of protein synthesis experimentally observed after fertilization (6.6-fold, SD = 2.3, n = 8). The minimal model was also used to simulate changes observed after fertilization in the presence of rapamycin, a FRAP/mTOR inhibitor. The model showed that the elF4E:4E-BP complex destabilization was impacted and surprisingly, that the mechanism of 4E-BP degradation was also strongly affected, therefore suggesting that both processes are controlled by the protein kinase FRAP/mTOR.
Tipo:  Text
Idioma:  Inglês

Editor:  Frontiers Media Sa
Formato:  application/pdf
Fonte:  Frontiers In Genetics (1664-8021) (Frontiers Media Sa), 2014-05 , Vol. 5 , N. 117 , P. 1-10
Direitos:  2014 Laurent, Richard, Mulner-Lorillon, Morales, Flament, Glippa, Bourdon, Gosselin, Siegel, Cormier and Bellé. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction ...


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