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Article Dans Une Revue iScience Année : 2021

Characteristic ERK1/2 signaling dynamics distinguishes necroptosis from apoptosis

Résumé

ERK1/2 involvement in cell death remains unclear, although many studies have demonstrated the importance of ERK1/2 dynamics in determining cellular responses. To untangle how ERK1/2 contributes to two cell death programs, we investigated ERK1/2 signaling dynamics during hFasL-induced apoptosis and TNF-induced necroptosis in L929 cells. We observed that ERK1/2 inhibition sensitizes cells to apoptosis while delaying necroptosis. By monitoring ERK1/2 activity by live-cell imaging using an improved ERK1/2 biosensor (EKAR4.0), we reported differential ERK1/2 signaling dynamics between cell survival, apoptosis, and necroptosis. We also decrypted a temporally shifted amplitude- and frequency-modulated (AM/FM) ERK1/2 activity profile in necroptosis versus apoptosis. ERK1/2 inhibition, which disrupted ERK1/2 signaling dynamics, prevented TNF and IL-6 gene expression increase during TNF-induced necroptosis. Using an inducible cell line for activated MLKL, the final executioner of necroptosis, we showed ERK1/2 and its distinctive necroptotic ERK1/2 activity dynamics to be positioned downstream of MLKL.

Domaines

Biophysique
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Dates et versions

hal-03795464 , version 1 (04-10-2022)

Identifiants

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François Sipieter, Benjamin Cappe, Aymeric Leray, Elke de Schutter, Jolien Bridelance, et al.. Characteristic ERK1/2 signaling dynamics distinguishes necroptosis from apoptosis. iScience, 2021, 24 (9), pp.103074. ⟨10.1016/j.isci.2021.103074⟩. ⟨hal-03795464⟩
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