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Title
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Characteristic ERK1/2 signaling dynamics distinguishes necroptosis from apoptosis
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Author
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Abstract
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| 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 apoptosiswhile delaying necroptosis. Bymonitoring 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. |
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Language
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English
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Source (journal)
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iScience
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Publication
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Elsevier
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2021
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ISSN
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2589-0042
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DOI
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10.1016/J.ISCI.2021.103074
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Volume/pages
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24
:9
(2021)
, 29 p.
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Article Reference
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103074
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ISI
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000698069100132
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Pubmed ID
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34568795
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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