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Mécanotransduction au cours du cycle cellulaire : Rôle de la déformation de l'enveloppe nucléaire

Abstract : .The shape of the cell nucleus can vary considerably during developmental and pathological processes as a consequence of the mechanical forces emanating from the microenvironment or generated by the cytoskeleton. However the impact of nuclear morphology on the transcriptional machinery is not known. Using a combination of tools to manipulate the nuclear morphology, we observed that changes in nuclear shape regulate the activity of AP1 and TEAD. We showed that nuclear flattening increases c-Jun phosphorylation and YAP nuclear translocation, leading to transcriptional induction of AP1 and TEAD-target genes. Surprisingly, we found that nuclear compression is necessary and sufficient to mediate c-Jun and YAP activation in response to cell- generated contractility or cell spreading. We additionally observed that nuclear flattening occurs during the cell cycle and promotes proliferation via TEAD and AP1- dependent G1 to S progression.
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Julien Aureille. Mécanotransduction au cours du cycle cellulaire : Rôle de la déformation de l'enveloppe nucléaire. Biologie cellulaire. Université Grenoble Alpes, 2018. Français. ⟨NNT : 2018GREAV072⟩. ⟨tel-02127487⟩

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