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Article Dans Une Revue Biomedicines Année : 2023

Myogenesis in C2C12 Cells Requires Phosphorylation of ATF6α by p38 MAPK

Résumé

Activating transcription factor 6α (ATF6α) is an endoplasmic reticulum protein known to participate in unfolded protein response (UPR) during ER stress in mammals. Herein, we show that in mouse C2C12 myoblasts induced to differentiate, ATF6α is the only pathway of the UPR activated. ATF6α stimulation is p38 MAPK-dependent, as revealed by the use of the inhibitor SB203580, which halts myotube formation and, at the same time, impairs trafficking of ATF6α, which accumulates at the cis-Golgi without being processed in the p50 transcriptional active form. To further evaluate the role of ATF6α, we knocked out the ATF6α gene, thus inhibiting the C2C12 myoblast from undergoing myogenesis, and this occurred independently from p38 MAPK activity. The expression of exogenous ATF6α in knocked-out ATF6α cells recover myogenesis, whereas the expression of an ATF6α mutant in the p38 MAPK phosphorylation site (T166) was not able to regain myogenesis. Genetic ablation of ATF6α also prevents the exit from the cell cycle, which is essential for muscle differentiation. Furthermore, when we inhibited differentiation by the use of dexamethasone in C2C12 cells, we found inactivation of p38 MAPK and, consequently, loss of ATF6α activity. All these findings suggest that the p-p38 MAPK/ATF6α axis, in pathophysiological conditions, regulates myogenesis by promoting the exit from the cell cycle, an essential step to start myoblasts differentiation.
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hal-04432202 , version 1 (12-02-2024)

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Valentina Pagliara, Giuseppina Amodio, Vincenzo Vestuto, Silvia Franceschelli, Nicola Antonino Russo, et al.. Myogenesis in C2C12 Cells Requires Phosphorylation of ATF6α by p38 MAPK. Biomedicines, 2023, 11 (5), pp.1457. ⟨10.3390/biomedicines11051457⟩. ⟨hal-04432202⟩
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