DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF‐κB

Rebsamen, Manuele; Heinz, Leonhard X.; Meylan, Etienne; Michallet, M; Schroder, Kate; Hofmann, Kay; Vázquez, Jessica; Benedict, Chris A.; Tschopp, Jürg

doi:10.1038/embor.2009.109

Cited by 316 publications

(329 citation statements)

References 25 publications

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“…112 DAI contains two RHIM motifs that allows it to interact with RIP1 and RIP3 and trigger downstream activation of NFkB 113,114 (Figure 3). The interaction of DAI with RIP3 also sensitizes cells to murine cytomegalovirus (MCMV)-induced necrosis with DAI-and RIP3-deficient cells being resistant to this form of death.…”

Section: Rip Kinases and Nucleic Acid Sensingmentioning

confidence: 99%

RIP kinases: key decision makers in cell death and innate immunity

et al. 2014

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Section: Rip Kinases and Nucleic Acid Sensingmentioning

confidence: 99%

RIP kinases: key decision makers in cell death and innate immunity

et al. 2014

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“…9A. The RHIM motif is known to mediate homotypic associations between signaling proteins involved in programmed necrosis and TLR signaling (42)(43)(44). Based on these observations, HeLa cells were co-transfected with plasmids encoding YFP-tagged PARP12⌬ZnF and tagged version of RHIM-containing proteins such as TRIF/TICAM1 (a Toll/IL1R domain containing signaling adaptor known to play a role in TLR signaling) and RIPK1 (an important kinase in several signaling pathways including NF-B activation).…”

Section: Co-localization and Physical Interaction Of Parp12 With Membmentioning

confidence: 99%

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

Welsby

Hutin

Gueydan

et al. 2014

Journal of Biological Chemistry

103

115

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Background:The individual role of members of the poly(ADP-ribose) polymerase family is unclear. Results: PARP12 displays a dual subcellular localization and effector function, controlling both protein translation and NF-B signaling. Conclusion: PARP12 mediates two important effector mechanisms linked to the establishment of an anti-viral state. Significance: ADP-ribosylation may play an important role in the innate control of microbial infections.

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“…[5][6][7] Physiological function of necroptosis has been illustrated in host defense, [8][9][10][11] inflammation, [12][13][14][15][16] tissue injury, 10,17,18 and development. [19][20][21] Necroptosis can be induced by a number of different extracellular stimuli such as tumor necrosis factor (TNF).…”

mentioning

confidence: 99%

Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis

et al. 2014

Cell Death Differ

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Necroptosis is mediated by a signaling complex called necrosome, containing receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like (MLKL). It is known that RIP1 and RIP3 form heterodimeric filamentous scaffold in necrosomes through their RIP homotypic interaction motif (RHIM) domain-mediated oligomerization, but the signaling events based on this scaffold has not been fully addressed. By using inducible dimer systems we found that RIP1-RIP1 interaction is dispensable for necroptosis; RIP1-RIP3 interaction is required for necroptosis signaling, but there is no necroptosis if no additional RIP3 protein is recruited to the RIP1-RIP3 heterodimer, and the interaction with RIP1 promotes the RIP3 to recruit other RIP3; RIP3-RIP3 interaction is required for necroptosis and RIP3-RIP3 dimerization is sufficient to induce necroptosis; and RIP3 dimer-induced necroptosis requires MLKL. We further show that RIP3 oligomer is not more potent than RIP3 dimer in triggering necroptosis, suggesting that RIP3 homo-interaction in the complex, rather than whether RIP3 has formed homo polymer, is important for necroptosis. RIP3 dimerization leads to RIP3 intramolecule autophosphorylation, which is required for the recruitment of MLKL. Interestingly, phosphorylation of one of RIP3 in the dimer is sufficient to induce necroptosis. As RIP1-RIP3 heterodimer itself cannot induce necroptosis, the RIP1-RIP3 heterodimeric amyloid fibril is unlikely to directly propagate necroptosis. We propose that the signaling events after the RIP1-RIP3 amyloid complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloid scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of MLKL by RIP3 to execute necroptosis. Cell Death and Differentiation (2014) 21, 1709-1720; doi:10.1038/cdd.2014.77; published online 6 June 2014Necroptosis is a type of programmed necrosis characterized by necrotic morphological changes, including cellular organelle swelling, cell membrane rupture, 1-3 and dependence of receptor-interacting protein (RIP)1 4 and RIP3. [5][6][7] Physiological function of necroptosis has been illustrated in host defense, [8][9][10][11] inflammation, 12-16 tissue injury, 10,17,18 and development. [19][20][21] Necroptosis can be induced by a number of different extracellular stimuli such as tumor necrosis factor (TNF). TNF stimulation leads to formation of TNF receptor 1 (TNFR1) signaling complex (named complex I), and complex II containing RIP1, TRADD, FAS-associated protein with a death domain (FADD), and caspase-8, of which the activation initiates apoptosis. If cells have high level of RIP3, RIP1 recruits RIP3 to form necrosome containing FADD, [22][23][24] caspase-8, RIP1, and RIP3, and the cells undergo necroptosis. 25,26 Caspase-8 and FADD negatively regulates necroptosis, 27-30 because RIP1, RIP3, and CYLD are potential substrates of caspase-8. [31][32][33][34] Necrosome also suppresses apoptosis but the underlying mechanism has not been described yet. Mixed-lineage kinase domain-like (ML...

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DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF‐κB

Cited by 316 publications

References 25 publications

RIP kinases: key decision makers in cell death and innate immunity

RIP kinases: key decision makers in cell death and innate immunity

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis

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