The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death
Open accessAbstract
TNF is an inflammatory cytokine that upon binding to its receptor, TNFR1, can drive cytokine production, cell survival, or cell death. TNFR1 stimulation causes activation of NF-κB, p38α, and its downstream effector kinase MK2, thereby promoting transcription, mRNA stabilization, and translation of target genes. Here we show that TNF-induced activation of MK2 results in global RIPK1 phosphorylation. MK2 directly phosphorylates RIPK1 at residue S321, which inhibits its ability to bind FADD/caspase-8 and induce RIPK1-kinase-dependent apoptosis and necroptosis. Consistently, a phospho-mimetic S321D RIPK1 mutation limits TNF-induced death. Mechanistically, we find that phosphorylation of S321 inhibits RIPK1 kinase activation. We further show that cytosolic RIPK1 contributes to complex-II-mediated cell death, independent of its recruitment to complex-I, suggesting that complex-II originates from both RIPK1 in complex-I and cytosolic RIPK1. Thus, MK2-mediated phosphorylation of RIPK1 serves as a checkpoint within the TNF signaling pathway that integrates cell survival and cytokine production.
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Citations
Cites
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Micheau, O., & Tschopp, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00521-x · Cited by 2,738
Direct observation of individual endogenous protein complexes in situ by proximity ligation
Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K.-J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L.-G., et al. (2006) · Nature Methods · doi:10.1038/nmeth947 · Cited by 2,419
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148
Self-citationIdentification of RIP1 kinase as a specific cellular target of necrostatins
Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I. L., Korkina, O., Teng, X., Abbott, D., Cuny, G. D., Yuan, C., Wagner, G., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.83 · Cited by 2,059
Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278 · cited 1×
“This inhibits formation of complex-II and the necrosome by cleaving RIPK1, RIPK3, and CYLD (Feng et al., 2007; Lin et al., 1999; O’Donnell et al., 2011; Oberst et al., 2011).”
BackgroundLi, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222
IAP Antagonists Induce Autoubiquitination of c-IAPs, NF-κB Activation, and TNFα-Dependent Apoptosis
Varfolomeev, E., Blankenship, J. W., Wayson, S. M., Fedorova, A. V., Kayagaki, N., Garg, P., Zobel, K., Dynek, J. N., Elliott, L. O., Wallweber, H. J. A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.030 · Cited by 1,218
Linear ubiquitination prevents inflammation and regulates immune signalling
Gerlach, B., Cordier, S. M., Schmukle, A. C., Emmerich, C. H., Rieser, E., Haas, T. L., Webb, A. I., Rickard, J. A., Anderton, H., Wong, W. W.-L., et al. (2011) · Nature · doi:10.1038/nature09816 · Cited by 940
Self-citation
Cited by
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationNecroptosis and RIPK1-mediated neuroinflammation in CNS diseases
Yuan, J., Amin, P., & Ofengeim, D. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0093-1 · Cited by 967
Diversity and versatility of p38 kinase signalling in health and disease
Canovas, B., & Nebreda, A. R. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00322-w · Cited by 657
TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging
Xu, D., Jin, T., Zhu, H., Chen, H., Ofengeim, D., Zou, C., Mifflin, L., Pan, L., Amin, P., Li, W., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.041 · Cited by 461
“RIPK1 is suppressed by inhibitory phosphorylations mediated directly by TAK1 and by the kinases activated by TAK1, including MK2 and IkB kinase (IKKs) (Dondelinger et al., 2015; Geng et al., 2017; Jaco et al., 2017; Menon et al., 2017).”
TBK1 and IKKε prevent TNF-induced cell death by RIPK1 phosphorylation
Lafont, E., Draber, P., Rieser, E., Reichert, M., Kupka, S., de Miguel, D., Draberova, H., von Mässenhausen, A., Bhamra, A., Henderson, S., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0229-6 · Cited by 283
Metadata
- Authors
- Jaco, I., Annibaldi, A., Lalaoui, N., Wilson, R., Tenev, T., Laurien, L., Kim, C., Jamal, K., Wicky John, S., Liccardi, G., Chau, D., Murphy, J. M., Brumatti, G., Feltham, R., Pasparakis, M., Silke, J., & Meier, P.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 66
- Issue
- 5
- Pages
- 698-710.e5
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2613123103
- Cited by
- 320
- References
- 15
- FWCI
- 10.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Jaco, I., Annibaldi, A., Lalaoui, N., Wilson, R., Tenev, T., Laurien, L., Kim, C., Jamal, K., Wicky John, S., Liccardi, G., Chau, D., Murphy, J. M., Brumatti, G., Feltham, R., Pasparakis, M., Silke, J., & Meier, P. (2017). MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death. Molecular Cell. https://doi.org/10.1016/j.molcel.2017.05.003
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