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Séminaire externe : Varun Chaudhar
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Le 22/09/2025, de 11:00 à 12:00 |
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| S'adresser à | Yad Ghavi-Helm |
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Séminaire externe : Varun Chaudhar (Associate Professor at IISER Bhopal, India)
"Regulation of the Unfolded Protein Response pathways by Drosophila Rer1 and its effect on competitive cell survival”
Résumé :
Cell competition, first identified in Drosophila epithelium, eliminates less fit cells via a juxtacrine fitness–sensing mechanism, thereby maintaining tissue integrity. A critical determinant of cellular fitness is proper ER protein homeostasis. Its disruption induces proteotoxic stress and activates the unfolded protein response pathways (UPR). While UPR activity is linked to the elimination of cells under stress, it is also observed in “super-competitor” cells, such as those overexpressing Myc, that overgrow by eliminating wildtype neighbours, despite being stressed. The mechanisms connecting cell competition to proteostasis regulation remain poorly understood.
We identify the ER- and Golgi-localized protein Rer1 as a key regulator of proteostasis and Myc-driven overgrowth. Loss of Rer1 activates the PERK and IRE1α branches of the UPR and triggers JNK signalling, with IRE1α activation occurring downstream of PERK. Importantly, in contrast to the typical cytoprotective role of UPR, this activation promotes cytotoxicity, suggesting that specific UPR branch interactions can switch the outcome from competitive survival to cell death. How stressed cells are recognized by their neighbours to initiate competition remains an intriguing open question.
Hôte : Yad Ghavi-Helm
Vendredi 22 septembre
Salle 063 IGFL