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Identification d'une nouvelle voie de signalisation impliquée dans la régulation des gènes par les acides aminés, chez les mammifères

Abstract : n mammals, environment is a powerful regulator of gene expression. For example, according to nutrition, nutrients -and particularly amino acids- availability is responsible for the induction of the expression of numerous genes. Indeed, specific molecular mechanisms are triggered in order to sense and respond adequately to these variations. Whenever one of the nine essential amino acids is missing, the transcription of specific genes is induced. This activation requires the induction of transcription factor ATF4 and the phosphorylation of transcription factor ATF2. The ATF4 pathway has been identified and relatively well described. However, the elements of the pathway upstream of ATF2 phosphorylation were yet unknown. The aim of my PhD thesis was to identify the different regulatory elements responsible for ATF2 phosphorylation in response to amino acid starvation. I have shown that amino acid starvation induces the activation of a MAPK module composed of MEKK1>MKK7>JNK2 that controls ATF2 phosphorylation on both threonine 69 and 71. I have shown that this module is regulated by two GTPases Cdc42+Rac1 and by Gα12. Finally, I was able to show that this new pathway is involved in the AARE-dependent transcription of ATF3 in response to an amino acid starvation.
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https://tel.archives-ouvertes.fr/tel-00726314
Contributor : Camille Meyer <>
Submitted on : Wednesday, August 29, 2012 - 3:52:08 PM
Last modification on : Tuesday, December 29, 2020 - 2:14:02 PM
Long-term archiving on: : Friday, December 16, 2016 - 8:42:06 AM

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  • HAL Id : tel-00726314, version 1
  • PRODINRA : 244621

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Cédric Chaveroux. Identification d'une nouvelle voie de signalisation impliquée dans la régulation des gènes par les acides aminés, chez les mammifères. Alimentation et Nutrition. Université d'Auvergne - Clermont-Ferrand I; Université Blaise Pascal - Clermont-Ferrand II, 2009. Français. ⟨NNT : 2009CLF1MM21⟩. ⟨tel-00726314⟩

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