PAVANI, Mattia; CHIROLI, Elena; CANCRINI, Camilla; GROSS, Fridolin; BONAIUTI, P.; VILLA, S.; GIAVAZZI, F.; MATAFORA, V.; BACHI, A.; FAVA, L.L.; LISCHETTI, T.; CILIBERTO, A.

doi:10.1016/j.celrep.2023.112215

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Article de revue

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Cell Reports. 2023, vol. 42, n° 3

Résumé en anglais

Drugs targeting microtubules rely on the mitotic checkpoint to arrest cell proliferation. The prolonged mitotic arrest induced by such drugs is followed by a G1 arrest. Here, we follow for several weeks the fate of G1-arrested human cells after treatment with nocodazole. We find that a small fraction of cells escapes from the arrest and resumes proliferation. These escaping cells experience reduced DNA damage and p21 activation. Cells surviving treatment are enriched for anti-apoptotic proteins, including Triap1. Increasing Triap1 levels allows cells to survive the first treatment with reduced DNA damage and lower levels of p21; accordingly, decreasing Triap1 re-sensitizes cells to nocodazole. We show that Triap1 upregulation leads to the retention of cytochrome c in the mitochondria, opposing the partial activation of caspases caused by nocodazole. In summary, our results point to a potential role of Triap1 upregulation in the emergence of resistance to drugs that induce prolonged mitotic arrest. © 2023 The Author(s)< Réduire

Mots clés en anglais

Cell cycle

Mitosis

Sublethal caspase activation

Microtubule targeting drugs

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https://oskar-bordeaux.fr/handle/20.500.12278/201354

DOI

http://dx.doi.org/10.1016/j.celrep.2023.112215

Unités de recherche

ImmunoConcEpT - UMR 5164

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Triap1 upregulation promotes escape from mitotic-slippage-induced G1 arrest

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Résumé en anglais

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