What question did this study set out to answer?

To determine how MK2 activation regulates RIPK1 activity and suppresses TNF-mediated programmed cell death pathways.

May 11, 2017Molecular CellOpen Access

MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death

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Authors

IJIsabel JacoNovartis (Switzerland)AAAlessandro AnnibaldiUniversity of Cologne NLNajoua LalaouiInserm

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Overview

Mechanistic study reveals that MK2 phosphorylates RIPK1 to block complex formation in cell models, indicating a critical survival checkpoint against TNF-driven apoptosis and necroptosis.

Key Points

To determine how MK2 activation regulates RIPK1 activity and suppresses TNF-mediated programmed cell death pathways.
Assessed TNF-mediated activation of the p38α-MK2 signaling cascade and characterized direct phosphorylation sites on RIPK1.
Engineered a phospho-mimetic S321D RIPK1 mutant to evaluate downstream RIPK1 kinase activation and binding affinity to FADD and caspase-8 death complexes.
MK2 directly phosphorylates RIPK1 at residue S321 following TNF stimulation, which blocks RIPK1 kinase activation and prevents association with FADD and caspase-8.
Expression of the phospho-mimetic S321D RIPK1 mutant prevents TNF-induced RIPK1-dependent apoptosis and necroptosis.
Cytosolic RIPK1 participates in complex-II assembly independently of complex-I recruitment, establishing MK2-dependent phosphorylation as a central checkpoint linking cytokine production and cell survival.

Cite This Study

Jaco et al. (2017) studied this question.

synapsesocial.com/papers/6a92e8bee62ac992d65c1889 https://doi.org/10.1016/j.molcel.2017.05.003

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May 11, 2017Molecular CellOpen Access

MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death

View Full Paper

Ask AI

Bookmark

Authors

IJIsabel JacoNovartis (Switzerland)AAAlessandro AnnibaldiUniversity of Cologne NLNajoua LalaouiInserm

Discussion

Member takes

Overview

Mechanistic study reveals that MK2 phosphorylates RIPK1 to block complex formation in cell models, indicating a critical survival checkpoint against TNF-driven apoptosis and necroptosis.

Key Points

To determine how MK2 activation regulates RIPK1 activity and suppresses TNF-mediated programmed cell death pathways.
Assessed TNF-mediated activation of the p38α-MK2 signaling cascade and characterized direct phosphorylation sites on RIPK1.
Engineered a phospho-mimetic S321D RIPK1 mutant to evaluate downstream RIPK1 kinase activation and binding affinity to FADD and caspase-8 death complexes.
MK2 directly phosphorylates RIPK1 at residue S321 following TNF stimulation, which blocks RIPK1 kinase activation and prevents association with FADD and caspase-8.
Expression of the phospho-mimetic S321D RIPK1 mutant prevents TNF-induced RIPK1-dependent apoptosis and necroptosis.
Cytosolic RIPK1 participates in complex-II assembly independently of complex-I recruitment, establishing MK2-dependent phosphorylation as a central checkpoint linking cytokine production and cell survival.

Cite This Study

Jaco et al. (2017) studied this question.

synapsesocial.com/papers/6a92e8bee62ac992d65c1889 https://doi.org/10.1016/j.molcel.2017.05.003

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