Ripk3

Summary

Gene Symbol: Ripk3
Description: receptor-interacting serine-threonine kinase 3
Alias: 2610528K09Rik, AW107945, Rip3, receptor-interacting serine/threonine-protein kinase 3, RIP-3, RIP-like protein kinase 3, mRIP3, receptor interacting protein 3
Species: mouse
Products:     Ripk3

Top Publications

  1. Khan N, Lawlor K, Murphy J, Vince J. More to life than death: molecular determinants of necroptotic and non-necroptotic RIP3 kinase signaling. Curr Opin Immunol. 2014;26:76-89 pubmed publisher
    Necroptosis describes a pro-inflammatory form of cell death governed by the kinases RIP1 and RIP3. Necroptosis can occur following stimulation of the DNA receptor, DAI, or activation of death receptor, Toll-like receptor, T-cell antigen ..
  2. Mandal P, Berger S, Pillay S, Moriwaki K, Huang C, Guo H, et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol Cell. 2014;56:481-95 pubmed publisher
    Receptor-interacting protein kinase 3 (RIP3 or RIPK3) has emerged as a central player in necroptosis and a potential target to control inflammatory disease...
  3. Philip N, Dillon C, Snyder A, Fitzgerald P, Wynosky Dolfi M, Zwack E, et al. Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling. Proc Natl Acad Sci U S A. 2014;111:7385-90 pubmed publisher
    ..caspase-8, receptor-interacting serine/threonine kinase 1 (RIPK1), and Fas-associated death domain (FADD), but not RIPK3. Furthermore, whereas RIPK3 deficiency did not affect YopJ-induced cell death or caspase-1 activation, deficiency ..
  4. Jouan Lanhouet S, Arshad M, Piquet Pellorce C, Martin Chouly C, Le Moigne Müller G, Van Herreweghe F, et al. TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation. Cell Death Differ. 2012;19:2003-14 pubmed publisher
    ..Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-..
  5. Lin J, Li H, Yang M, Ren J, Huang Z, Han F, et al. A role of RIP3-mediated macrophage necrosis in atherosclerosis development. Cell Rep. 2013;3:200-10 pubmed publisher
    ..role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3(-/-);Ldlr(-/-) mice were no different from RIP3(+/+);Ldlr(-/-) mice in early atherosclerosis but had significant ..
  6. Upton J, Kaiser W, Mocarski E. Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe. 2010;7:302-13 pubmed publisher
    ..We find that murine cytomegalovirus infection induces RIP3-dependent necrosis...
  7. Trichonas G, Murakami Y, Thanos A, Morizane Y, Kayama M, Debouck C, et al. Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis. Proc Natl Acad Sci U S A. 2010;107:21695-700 pubmed publisher
    ..b>RIP3 expression, a key activator of RIP1 kinase, increased more than 10-fold after retinal detachment...
  8. Newton K, Sun X, Dixit V. Kinase RIP3 is dispensable for normal NF-kappa Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol Cell Biol. 2004;24:1464-9 pubmed
    b>RIP3 is a member of the RIP kinase family. It is expressed in the embryo and in multiple adult tissues, including most hemopoietic cell lineages...
  9. Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012;148:228-43 pubmed publisher
    ..necrosis induced by TNF-? requires the activities of the receptor-interacting serine-threonine kinases RIP1 and RIP3 and their interaction with the mixed lineage kinase domain-like protein MLKL...

More Information

Publications75

  1. He S, Liang Y, Shao F, Wang X. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci U S A. 2011;108:20054-9 pubmed publisher
    We report here that mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-?-independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I:C) and LPS, respectively...
  2. Lu J, Weist B, van Raam B, Marro B, Nguyen L, Srinivas P, et al. Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity. Proc Natl Acad Sci U S A. 2011;108:15312-7 pubmed publisher
    ..Recent studies have demonstrated that receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3 together facilitate TNF-induced necroptosis, but the precise role of RIPKs in the demise of T cells lacking FADD ..
  3. Weng D, Marty Roix R, Ganesan S, Proulx M, Vladimer G, Kaiser W, et al. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. Proc Natl Acad Sci U S A. 2014;111:7391-6 pubmed publisher
    ..Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1?, IL-18, TNF, and IL-6; impaired activation of the ..
  4. Zhang D, Shao J, Lin J, Zhang N, Lu B, Lin S, et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 2009;325:332-6 pubmed publisher
    ..We identified the protein kinase receptor-interacting protein 3 (RIP3) as a molecular switch between TNF-induced apoptosis and necrosis in NIH 3T3 cells and found that RIP3 was required ..
  5. Wang H, Sun L, Su L, Rizo J, Liu L, Wang L, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell. 2014;54:133-146 pubmed publisher
    ..TNF-?) family of cytokines is dependent on a kinase cascade consisting of receptor-interacting kinases RIP1 and RIP3. How these kinase activities cause cells to die by necrosis is not known...
  6. Newton K, Dugger D, Wickliffe K, Kapoor N, de Almagro M, Vucic D, et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science. 2014;343:1357-60 pubmed publisher
    Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 trigger pro-inflammatory cell death termed "necroptosis...
  7. O Donnell M, Perez Jimenez E, Oberst A, Ng A, Massoumi R, Xavier R, et al. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat Cell Biol. 2011;13:1437-42 pubmed publisher
    ..8 is to transmit a pro-survival signal that suppresses programmed necrosis (or necroptosis) mediated by RIPK1 and RIPK3 (refs 2-6) during embryogenesis and haematopoiesis(7-9)...
  8. Murphy J, Czabotar P, Hildebrand J, Lucet I, Zhang J, Alvarez Diaz S, et al. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity. 2013;39:443-53 pubmed publisher
    ..essential nonenzymatic role in necroptotic signaling is induced by receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated phosphorylation...
  9. Kaiser W, Upton J, Long A, Livingston Rosanoff D, Daley Bauer L, Hakem R, et al. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 2011;471:368-72 pubmed publisher
    ..Casp8 suppresses RIP3-RIP1 (also known as RIPK3-RIPK1) kinase complex-dependent necroptosis that follows death receptor activation as well as a RIP3-dependent, ..
  10. Vanlangenakker N, Vanden Berghe T, Bogaert P, Laukens B, Zobel K, Deshayes K, et al. cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ. 2011;18:656-65 pubmed publisher
    ..accompanied by enhanced RIP1 kinase activity, increased recruitment of RIP1 to Fas-associated via death domain and RIP3 (which allows necrosome formation), and elevated RIP1 kinase-dependent accumulation of reactive oxygen species (ROS)..
  11. Moriwaki K, Balaji S, McQuade T, Malhotra N, Kang J, Chan F. The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair. Immunity. 2014;41:567-78 pubmed publisher
    ..is an inflammatory form of cell death that critically requires the receptor-interacting protein kinase 3 (RIPK3)...
  12. He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009;137:1100-11 pubmed publisher
    ..A genome wide siRNA screen revealed another member of the RIP kinase family, RIP3, to be required for necrosis...
  13. Wong W, Vince J, Lalaoui N, Lawlor K, Chau D, Bankovacki A, et al. cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1- and RIPK3-dependent manner. Blood. 2014;123:2562-72 pubmed publisher
    ..The loss of RIPK1 or RIPK3, but not the RIPK3 substrate mixed lineage kinase domain-like protein, attenuated TNF secretion and thereby ..
  14. Ramachandran A, McGill M, Xie Y, Ni H, Ding W, Jaeschke H. Receptor interacting protein kinase 3 is a critical early mediator of acetaminophen-induced hepatocyte necrosis in mice. Hepatology. 2013;58:2099-108 pubmed publisher
    ..Recent findings suggest that the receptor interacting protein kinase 3 (RIP3) acts as a switch from apoptosis to necrosis (programmed necrosis)...
  15. Kang T, Yang S, Tóth B, Kovalenko A, Wallach D. Caspase-8 blocks kinase RIPK3-mediated activation of the NLRP3 inflammasome. Immunity. 2013;38:27-40 pubmed publisher
    ..for this inflammation is enhanced signaling for necrotic cell death, mediated by the protein kinases RIPK1 and RIPK3 that caspase-8 can cleave...
  16. Oberst A, Dillon C, Weinlich R, McCormick L, Fitzgerald P, Pop C, et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 2011;471:363-7 pubmed publisher
    ..of caspase-8-deficient mice is completely rescued by ablation of receptor interacting protein kinase-3 (RIPK3)...
  17. Zhang H, Zhou X, McQuade T, Li J, Chan F, Zhang J. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature. 2011;471:373-6 pubmed publisher
    ..Therefore, our data demonstrate an unexpected cell-type-specific interplay between FADD and RIP1, which is critical for the regulation of apoptosis and necrosis during embryogenesis and lymphocyte function. ..
  18. Dillon C, Weinlich R, Rodriguez D, Cripps J, Quarato G, Gurung P, et al. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell. 2014;157:1189-202 pubmed publisher
    Receptor-interacting protein kinase (RIPK)-1 is involved in RIPK3-dependent and -independent signaling pathways leading to cell death and/or inflammation...
  19. Upton J, Kaiser W, Mocarski E. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe. 2012;11:290-7 pubmed publisher
    ..Receptor-interacting protein kinase (RIP) 3 (also called RIPK3) mediates RIP homotypic interaction motif (RHIM)-dependent programmed necrosis induced by murine cytomegalovirus (..
  20. Duprez L, Takahashi N, Van Hauwermeiren F, Vandendriessche B, Goossens V, Vanden Berghe T, et al. RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity. 2011;35:908-18 pubmed publisher
    ..However, deletion of RIPK3 conferred complete protection against lethal SIRS and reduced the amounts of circulating damage-associated ..
  21. Wu J, Huang Z, Ren J, Zhang Z, He P, Li Y, et al. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res. 2013;23:994-1006 pubmed publisher
    Mixed lineage kinase domain-like protein (Mlkl) was recently found to interact with receptor interacting protein 3 (Rip3) and to be essential for tumor necrosis factor (TNF)-induced programmed necrosis (necroptosis) in cultured cell lines...
  22. Kaiser W, Sridharan H, Huang C, Mandal P, Upton J, Gough P, et al. Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J Biol Chem. 2013;288:31268-79 pubmed publisher
    ..necrosis through a RIP homotypic interaction motif-dependent association of TRIF with RIP3 kinase (also called RIPK3)...
  23. Yabal M, Muller N, Adler H, Knies N, Groß C, Damgaard R, et al. XIAP restricts TNF- and RIP3-dependent cell death and inflammasome activation. Cell Rep. 2014;7:1796-808 pubmed publisher
    ..Aberrant IL-1? secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2...
  24. Moulin M, Anderton H, Voss A, Thomas T, Wong W, Bankovacki A, et al. IAPs limit activation of RIP kinases by TNF receptor 1 during development. EMBO J. 2012;31:1679-91 pubmed publisher
    ..Similarly, deletion of Ripk3 was able to rescue the mid-gestation defect of cIap2(-/-)cIap1(-/-) embryos, as these embryos survived to E15.5...
  25. Vucur M, Reisinger F, Gautheron J, Janssen J, Roderburg C, Cardenas D, et al. RIP3 inhibits inflammatory hepatocarcinogenesis but promotes cholestasis by controlling caspase-8- and JNK-dependent compensatory cell proliferation. Cell Rep. 2013;4:776-90 pubmed publisher
    ..However, it was recently discovered that receptor interacting protein 3 (RIP3)-dependent "necroptosis" represents an alternative programmed cell death pathway ..
  26. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148:213-27 pubmed publisher
    The receptor-interacting serine-threonine kinase 3 (RIP3) is a key signaling molecule in the programmed necrosis (necroptosis) pathway...
  27. Ch en I, Tsau J, Molkentin J, Komatsu M, Hedrick S. Mechanisms of necroptosis in T cells. J Exp Med. 2011;208:633-41 pubmed publisher
    ..Additionally, complementation of a T cell-specific caspase 8 deficiency with a loss of Ripk3 gives rise to lymphoproliferative disease reminiscent of lpr or gld mice...
  28. Dillon C, Oberst A, Weinlich R, Janke L, Kang T, Ben Moshe T, et al. Survival function of the FADD-CASPASE-8-cFLIP(L) complex. Cell Rep. 2012;1:401-7 pubmed
    ..Recent studies have shown that development in caspase-8-deficient mice is rescued by ablation of RIPK3, a kinase that promotes a form of programmed, necrotic cell death...
  29. Bonnet M, Preukschat D, Welz P, Van Loo G, Ermolaeva M, Bloch W, et al. The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation. Immunity. 2011;35:572-82 pubmed publisher
    ..The development of skin inflammation in FADD(E-KO) mice was triggered by RIP kinase 3 (RIP3)-mediated programmed necrosis (termed necroptosis) of FADD-deficient keratinocytes, which was partly dependent on ..
  30. Kaiser W, Daley Bauer L, Thapa R, Mandal P, Berger S, Huang C, et al. RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proc Natl Acad Sci U S A. 2014;111:7753-8 pubmed publisher
    ..interacting protein (RIP1, also called RIPK1) mediates programmed necrosis and, together with its partner, RIP3 (RIPK3), drives midgestational death of caspase 8 (Casp8)-deficient embryos...
  31. Linkermann A, Bräsen J, Darding M, Jin M, Sanz A, Heller J, et al. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2013;110:12024-9 pubmed publisher
    ..injury (IRI) in mice occurs as primary organ damage, independent of the immune system, and that mice deficient for RIPK3, the essential downstream partner of RIPK1 in necroptosis, are protected from IRI...
  32. Vince J, Wong W, Gentle I, Lawlor K, Allam R, O Reilly L, et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity. 2012;36:215-27 pubmed publisher
    ..rapid and full generation of active IL-1? by the NLRP3-caspase-1 inflammasome, or by caspase-8, required the kinase RIP3 and reactive oxygen species production...
  33. Luedde M, Lutz M, Carter N, Sosna J, Jacoby C, Vucur M, et al. RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction. Cardiovasc Res. 2014;103:206-16 pubmed publisher
    ..in programmed necrosis has been attributed to interactions of the receptor-interacting protein kinases, RIP1 and RIP3. However, the specific functional role of RIP3-dependent signalling and necroptosis in the heart is unknown...
  34. Allam R, Lawlor K, Yu E, Mildenhall A, Moujalled D, Lewis R, et al. Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Rep. 2014;15:982-90 pubmed publisher
  35. Welz P, Wullaert A, Vlantis K, Kondylis V, Fernández Majada V, Ermolaeva M, et al. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature. 2011;477:330-4 pubmed publisher
    ..Genetic deficiency in RIP3, a critical regulator of programmed necrosis, prevented the development of spontaneous pathology in both the small ..
  36. Cho Y, Challa S, Moquin D, Genga R, Ray T, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112-23 pubmed publisher
    ..Using a RNA interference screen, we identified the kinase RIP3 as a crucial activator for programmed necrosis induced by TNF and during virus infection...
  37. Wang X, Jiang W, Yan Y, Gong T, Han J, Tian Z, et al. RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway. Nat Immunol. 2014;15:1126-33 pubmed publisher
    ..Here we found that inhibition of the serine-threonine kinases RIP1 (RIPK1) or RIP3 (RIPK3) suppressed RNA virus-induced activation of the NLRP3 inflammasome...
  38. Hildebrand J, Tanzer M, Lucet I, Young S, Spall S, Sharma P, et al. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci U S A. 2014;111:15072-7 pubmed publisher
    ..in the necroptotic cell death pathway downstream of the protein kinase Receptor Interacting Protein Kinase-3 (RIPK3)...
  39. Robinson N, McComb S, Mulligan R, Dudani R, Krishnan L, Sad S. Type I interferon induces necroptosis in macrophages during infection with Salmonella enterica serovar Typhimurium. Nat Immunol. 2012;13:954-62 pubmed publisher
    ..Specific inhibition of the kinase RIP1 or knockdown of the gene encoding the kinase RIP3 prevented the death of wild-type macrophages, which indicated that necroptosis was a mechanism of cell death...
  40. Deutsch M, Graffeo C, Rokosh R, Pansari M, Ochi A, Levie E, et al. Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury. Cell Death Dis. 2015;6:e1759 pubmed publisher
    ..The roles of RIP1 and RIP3 in mediating hepatocyte death from acute liver injury are incompletely defined...
  41. Murakami Y, Matsumoto H, Roh M, Suzuki J, Hisatomi T, Ikeda Y, et al. Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration. Proc Natl Acad Sci U S A. 2012;109:14598-603 pubmed publisher
    ..The expression of RIP3, a key regulator of programmed necrosis, was elevated in rd10 mouse retinas in the phase of cone but not rod ..
  42. Silke J, Rickard J, Gerlic M. The diverse role of RIP kinases in necroptosis and inflammation. Nat Immunol. 2015;16:689-97 pubmed publisher
    ..Necroptosis was originally defined as being dependent on the kinase RIPK1 but is now known to be dependent on RIPK3 and the pseudo-kinase MLKL. Therefore, RIPK1, RIPK3 and MLKL are potential therapeutic targets...
  43. Kang Y, Bang B, Han K, Hong L, Shim E, Ma J, et al. Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling. Nat Commun. 2015;6:8371 pubmed publisher
    The receptor-interacting protein kinase 3 (RIPK3) plays crucial roles in programmed necrosis and innate inflammatory responses. However, a little is known about the involvement of RIPK3 in NKT cell-mediated immune responses...
  44. Yang Z, Jiang B, Wang Y, Ni H, Zhang J, Xia J, et al. 2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter. Cell Rep. 2017;19:1846-1857 pubmed publisher
    ..DNMT1-dependent hypermethylation of the RIP3 promoter occurred in both IDH1 R132Q knockin mutant mouse embryonic fibroblast (MEFs) and 2-HG-treated wild-type (..
  45. Xie T, Peng W, Yan C, Wu J, Gong X, Shi Y. Structural insights into RIP3-mediated necroptotic signaling. Cell Rep. 2013;5:70-8 pubmed publisher
    b>RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown...
  46. Roderick J, Hermance N, Zelic M, Simmons M, Polykratis A, Pasparakis M, et al. Hematopoietic RIPK1 deficiency results in bone marrow failure caused by apoptosis and RIPK3-mediated necroptosis. Proc Natl Acad Sci U S A. 2014;111:14436-41 pubmed publisher
    ..We demonstrate that RIPK3 deficiency partially rescues hematopoiesis in Vav-iCre Ripk1(fl/fl) mice, showing that RIPK1-deficient ..
  47. Li L, Chen Y, Doan J, Murray J, Molkentin J, Liu Q. Transforming growth factor β-activated kinase 1 signaling pathway critically regulates myocardial survival and remodeling. Circulation. 2014;130:2162-72 pubmed publisher
    ..RIP 1 (receptor-interacting protein 1)-FADD (Fas-associated protein with death domain)-caspase 8 and RIP1-RIP3, a process that is dependent on FADD and caspase 8 as scaffolding molecules...
  48. Chen W, Zhou Z, Li L, Zhong C, Zheng X, Wu X, et al. Diverse sequence determinants control human and mouse receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) interaction in necroptotic signaling. J Biol Chem. 2013;288:16247-61 pubmed publisher
    b>Receptor interacting protein 3 (RIP3) is a protein kinase essential for TNF-induced necroptosis...
  49. Schreiber A, Rousselle A, Becker J, von Mässenhausen A, Linkermann A, Kettritz R. Necroptosis controls NET generation and mediates complement activation, endothelial damage, and autoimmune vasculitis. Proc Natl Acad Sci U S A. 2017;114:E9618-E9625 pubmed publisher
    ..RIPK1 inhibitors are currently being evaluated in clinical trials and exhibit a novel therapeutic strategy in AAV. ..
  50. McQuade T, Cho Y, Chan F. Positive and negative phosphorylation regulates RIP1- and RIP3-induced programmed necrosis. Biochem J. 2013;456:409-15 pubmed publisher
    ..serine/threonine kinases, RIP1 (receptor-interacting serine/threonine protein kinase 1; also known as RIPK1) and RIP3. The phosphorylation of RIP1 and RIP3 is critical for assembly of the necrosome, an amyloid-like complex that ..
  51. Cook W, Moujalled D, Ralph T, Lock P, Young S, Murphy J, et al. RIPK1- and RIPK3-induced cell death mode is determined by target availability. Cell Death Differ. 2014;21:1600-12 pubmed publisher
    Both receptor-interacting protein kinase 1 (RIPK1) and RIPK3 can signal cell death following death receptor ligation...
  52. Matsuoka Y, Tsujimoto Y. Role of RIP1 in physiological enterocyte turnover in mouse small intestine via nonapoptotic death. Genes Cells. 2015;20:11-28 pubmed publisher
    ..Unlike Nec-1-sensitive (RIP1-dependent) cell death, so called necroptosis, which is also dependent on RIP3, physiological enterocyte turnover in RIP3-deficient mice was executed normally and still inhibited by Nec-1...
  53. Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 2014;513:90-4 pubmed publisher
    ..RIPK1 is implicated in inflammatory and cell death signalling and its kinase activity is believed to drive RIPK3-mediated necroptosis...
  54. Pavlosky A, Lau A, Su Y, Lian D, Huang X, Yin Z, et al. RIPK3-mediated necroptosis regulates cardiac allograft rejection. Am J Transplant. 2014;14:1778-90 pubmed publisher
    ..group box 1 (HMGB1) were inhibited by the RIPK1 inhibiting molecule necrostatin-1 and by genetic deletion of RIPK3. In addition, tissue necrosis, release of HMGB1 and graft cell infiltrate were attenuated in RIPK3 null heart ..
  55. Chen L, Liu X, Yu X, Ren R, Wang C, Zhao R, et al. Chlamydia muridarum Infection of Macrophages Stimulates IL-1β Secretion and Cell Death via Activation of Caspase-1 in an RIP3-Independent Manner. Biomed Res Int. 2017;2017:1592365 pubmed publisher
    ..b>RIP3 is a molecular switch that determines the development of necrosis or inflammation...
  56. Pazdernik N, Donner D, Goebl M, Harrington M. Mouse receptor interacting protein 3 does not contain a caspase-recruiting or a death domain but induces apoptosis and activates NF-kappaB. Mol Cell Biol. 1999;19:6500-8 pubmed
    ..Based upon domain organization and sequence similarity, this novel kinase, named mRIP3 (mouse receptor interacting protein 3), appears to be a new RIP family member...
  57. Tortola L, Nitsch R, Bertrand M, Kogler M, Redouane Y, Kozieradzki I, et al. The Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate. Cell Rep. 2016;15:1481-1492 pubmed publisher
    ..Intriguingly, loss of HACE1 does not impair TNFR1-mediated necroptotic cell fate via RIP1 and RIP3 kinases...
  58. Yamada T, Adachi Y, Fukaya M, Iijima M, Sesaki H. Dynamin-Related Protein 1 Deficiency Leads to Receptor-Interacting Protein Kinase 3-Mediated Necroptotic Neurodegeneration. Am J Pathol. 2016;186:2798-2802 pubmed publisher
    ..by generating Purkinje cell-specific Drp1-knockout (KO) mice that lack the receptor-interacting protein kinase 3 (Rip3), which regulates necroptosis...
  59. McGill M, Du K, Xie Y, Bajt M, Ding W, Jaeschke H. The role of the c-Jun N-terminal kinases 1/2 and receptor-interacting protein kinase 3 in furosemide-induced liver injury. Xenobiotica. 2015;45:442-9 pubmed publisher
    ..500 mg FS/kg bodyweight, and c-Jun N-terminal kinase (JNK) activation and receptor-interacting protein kinase 3 (RIP3) expression were measured by western blotting...
  60. Kondylis V, Polykratis A, Ehlken H, Ochoa Callejero L, Straub B, Krishna Subramanian S, et al. NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis. Cancer Cell. 2015;28:582-598 pubmed publisher
    ..Collectively, these results show that NEMO prevents hepatocarcinogenesis by inhibiting RIPK1 kinase activity-driven hepatocyte apoptosis through NF-κB-dependent and -independent functions. ..
  61. Schock S, Young J, He T, Sun Y, Winoto A. Deletion of FADD in macrophages and granulocytes results in RIP3- and MyD88-dependent systemic inflammation. PLoS ONE. 2015;10:e0124391 pubmed publisher
    ..These phenotypes were abolished when RIP3 deficiency was introduced, suggesting that systemic inflammation is caused by RIP3-dependent necroptotic and/or ..
  62. Gurung P, Burton A, Kanneganti T. NLRP3 inflammasome plays a redundant role with caspase 8 to promote IL-1?-mediated osteomyelitis. Proc Natl Acad Sci U S A. 2016;113:4452-7 pubmed publisher
    ..In conclusion, our studies have uncovered the combined actions of the NLRP3 inflammasome and caspase 8 leading to IL-1? maturation and the directionality of IL-1? in driving disease inPstpip2(cmo)mice. ..
  63. Yao Y, Chen S, Cao M, Fan X, Yang T, Huang Y, et al. Antigen-specific CD8+ T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin. Nat Commun. 2017;8:15402 pubmed publisher
    ..Our study reveals a positive feedback loop between antigen-specific CTLs and APC to amplify adaptive immunity. ..
  64. McComb S, Cessford E, Alturki N, Joseph J, Shutinoski B, Startek J, et al. Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages. Proc Natl Acad Sci U S A. 2014;111:E3206-13 pubmed publisher
    ..adaptor inducing IFN-? (TRIF) and led to persistent phosphorylation of receptor-interacting protein 3 (Rip3) kinase, which resulted in potent necroptosis...
  65. Schneider A, Gautheron J, Feoktistova M, Roderburg C, Loosen S, Roy S, et al. RIPK1 Suppresses a TRAF2-Dependent Pathway to Liver Cancer. Cancer Cell. 2017;31:94-109 pubmed publisher
    ..In line, low RIPK1 and TRAF2 expression in human HCCs was associated with an unfavorable prognosis, suggesting that RIPK1 collaborates with TRAF2 to inhibit murine and human hepatocarcinogenesis. ..
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    ..Pull down experiments with biotinylated Sorafenib show that it binds independently RIPK1, RIPK3 and MLKL. Moreover, it inhibits RIPK1 and RIPK3 kinase activity...