Gene Symbol: Ripk1
Description: receptor (TNFRSF)-interacting serine-threonine kinase 1
Alias: D330015H01Rik, RIP, RIP-1, Rinp, Rip1, receptor-interacting serine/threonine-protein kinase 1, cell death protein RIP, receptor-interacting protein 1, serine/threonine-protein kinase RIP
Species: mouse
Products:     Ripk1

Top Publications

  1. Lee T, Shank J, Cusson N, Kelliher M. The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J Biol Chem. 2004;279:33185-91 pubmed
    The death domain kinase Rip1 is recruited to the tumor necrosis factor receptor type 1 and mediates the IkappaB kinase and p38 MAP kinase pathways...
  2. 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
    ..The kinase RIP1 is crucial for programmed necrosis, but also mediates activation of the prosurvival transcription factor NF-kappaB...
  3. Kelliher M, Grimm S, Ishida Y, Kuo F, Stanger B, Leder P. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity. 1998;8:297-303 pubmed
    The death domain serine/threonine kinase RIP interacts with the death receptors Fas and tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis, SAPK/JNK, and NF-kappaB activation...
  4. Wright A, Reiley W, Chang M, Jin W, Lee A, Zhang M, et al. Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD. Dev Cell. 2007;13:705-16 pubmed
    ..We further show that CYLD negatively regulates a ubiquitin-dependent NF-kappaB activator, RIP1. CYLD binds to RIP1 and inhibits its ubiquitination and signaling function...
  5. Devin A, Lin Y, Liu Z. The role of the death-domain kinase RIP in tumour-necrosis-factor-induced activation of mitogen-activated protein kinases. EMBO Rep. 2003;4:623-7 pubmed
    The death-domain kinase RIP (receptor-interacting protein) is an important effector of tumour necrosis factor (TNF) signalling and is essential for TNF-induced nuclear factor-kappaB activation...
  6. O Donnell M, Legarda Addison D, Skountzos P, Yeh W, Ting A. Ubiquitination of RIP1 regulates an NF-kappaB-independent cell-death switch in TNF signaling. Curr Biol. 2007;17:418-24 pubmed
    ..We show that lysine 63-linked ubiquitination of RIP1 on lysine 377 inhibits TNF-induced apoptosis first through an NF-kappaB-independent mechanism and, subsequently, ..
  7. 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, RIP1-..
  8. Xu G, Tan X, Wang H, Sun W, Shi Y, Burlingame S, et al. Ubiquitin-specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear factor kappaB activation via binding to and deubiquitinating receptor-interacting protein 1. J Biol Chem. 2010;285:969-78 pubmed publisher
    Ubiquitination and deubiquitination of receptor-interacting protein 1 (RIP1) play an important role in the positive and negative regulation of the tumor necrosis factor alpha (TNFalpha)-induced nuclear factor kappaB (NF-kappaB) activation...
  9. Haas T, Emmerich C, Gerlach B, Schmukle A, Cordier S, Rieser E, et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell. 2009;36:831-44 pubmed publisher
    ..linkage types and that its recruitment to the TNF-RSC is impaired in TRADD-, TRAF2-, and cIAP1/2- but not in RIP1- or NEMO-deficient MEFs...

More Information


  1. 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
    ..but block apoptosis by functioning as E3 ligases for effector caspases and receptor-interacting protein 1 (RIP1)...
  2. Gentle I, Wong W, Evans J, Bankovacki A, Cook W, Khan N, et al. In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-kappaB and activation of caspase-8. J Biol Chem. 2011;286:13282-91 pubmed publisher
    b>RIPK1 is involved in signaling from TNF and TLR family receptors. After receptor ligation, RIPK1 not only modulates activation of both canonical and NIK-dependent NF-?B, but also regulates caspase-8 activation and cell death...
  3. Wu C, Conze D, Li T, Srinivasula S, Ashwell J. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat Cell Biol. 2006;8:398-406 pubmed
    ..attachment of Lys 63-linked polyubiquitin chains to signalling intermediates such as receptor-interacting protein (RIP)...
  4. 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
    ..FADD could directly bind to RIP1 (also known as RIPK1), a serine/threonine kinase that mediates both necrosis and NF-?B activation...
  5. 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...
  6. 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
    ..Typhimurium-induced cell death. Specific inhibition of the kinase RIP1 or knockdown of the gene encoding the kinase RIP3 prevented the death of wild-type macrophages, which indicated ..
  7. 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
    ..These compounds interact with RIP3 to activate caspase 8 (Casp8) via RHIM-driven recruitment of RIP1 (RIPK1) to assemble a Casp8-FADD-cFLIP complex completely independent of pronecrotic kinase activities and MLKL...
  8. 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
    ..of caspase 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)...
  9. 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
    ..RIP3 did not affect RIP1-mediated apoptosis but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase ..
  10. Shen H, Lin Y, Choksi S, Tran J, Jin T, Chang L, et al. Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death. Mol Cell Biol. 2004;24:5914-22 pubmed
    ..Data from this study suggest that receptor-interacting protein (RIP) and tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2), two key effector molecules of TNF signaling,..
  11. Festjens N, Vanden Berghe T, Cornelis S, Vandenabeele P. RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell Death Differ. 2007;14:400-10 pubmed
    ..b>RIP1 is a crucial adaptor kinase on the crossroad of these stress-induced signalling pathways and a cell's decision to ..
  12. Vivarelli M, McDonald D, Miller M, Cusson N, Kelliher M, Geha R. RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation. J Exp Med. 2004;200:399-404 pubmed
    Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis-associated factor (TRAF)2 and TRAF6...
  13. Rickard J, O Donnell J, Evans J, Lalaoui N, Poh A, Rogers T, et al. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell. 2014;157:1175-88 pubmed publisher
    Upon ligand binding, RIPK1 is recruited to tumor necrosis factor receptor superfamily (TNFRSF) and Toll-like receptor (TLR) complexes promoting prosurvival and inflammatory signaling...
  14. 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
    ..Genetic ablation of ripk1 causes postnatal lethality, which was not prevented by deletion of ripk3, caspase-8, or fadd...
  15. 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
  16. Wong W, Gentle I, Nachbur U, Anderton H, Vaux D, Silke J. RIPK1 is not essential for TNFR1-induced activation of NF-kappaB. Cell Death Differ. 2010;17:482-7 pubmed publisher
    On TNF binding, receptor-interacting protein kinase 1 (RIPK1) is recruited to the cytoplasmic domain of TNFR1, at which it becomes ubiquitylated and serves as a platform for recruitment and activation of NEMO/IKK1/IKK2 and TAK1/TAB2...
  17. Petersen S, Wang L, Yalcin Chin A, Li L, Peyton M, Minna J, et al. Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell. 2007;12:445-56 pubmed
    ..In response to autocrine TNFalpha signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.
  18. Stanger B, Leder P, Lee T, Kim E, Seed B. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell. 1995;81:513-23 pubmed
    ..products that associate with the intracellular domain of Fas: Fas itself, and a novel 74 kDa protein we have named RIP, for receptor interacting protein...
  19. Linkermann A, Bräsen J, Himmerkus N, Liu S, Huber T, Kunzendorf U, et al. Rip1 (receptor-interacting protein kinase 1) mediates necroptosis and contributes to renal ischemia/reperfusion injury. Kidney Int. 2012;81:751-61 pubmed publisher
    ..Necrostatin-1 may have therapeutic potential to prevent and treat renal ischemia/reperfusion injury. ..
  20. 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
    ..RIP3 expression, a key activator of RIP1 kinase, increased more than 10-fold after retinal detachment...
  21. Chen N, Chio I, Lin W, Duncan G, Chau H, Katz D, et al. Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors. Proc Natl Acad Sci U S A. 2008;105:12429-34 pubmed publisher
    ..Thus, TRADD is a multifunctional protein crucial both for TNFR1 signaling and other signaling pathways relevant to immune responses. ..
  22. Lin Y, Yang Q, Wang X, Liu Z. The essential role of the death domain kinase receptor-interacting protein in insulin growth factor-I-induced c-Jun N-terminal kinase activation. J Biol Chem. 2006;281:23525-32 pubmed
    ..Here, we show that the receptor-interacting protein (RIP), a key mediator of tumor necrosis factor-induced NF-kappaB and JNK activation, plays a key role in IGF-I receptor ..
  23. Cusson N, Oikemus S, Kilpatrick E, Cunningham L, Kelliher M. The death domain kinase RIP protects thymocytes from tumor necrosis factor receptor type 2-induced cell death. J Exp Med. 2002;196:15-26 pubmed
    ..The death domain kinase, receptor interacting protein (rip), is recruited to the TNFR1 upon receptor activation...
  24. Vince J, Wong W, Khan N, Feltham R, Chau D, Ahmed A, et al. IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell. 2007;131:682-93 pubmed
    ..Cells treated with an IAC, or those in which cIAP1 was deleted, became sensitive to apoptosis induced by exogenous TNFalpha, suggesting novel uses of these compounds in treating cancer. ..
  25. Christofferson D, Li Y, Hitomi J, Zhou W, Upperman C, Zhu H, et al. A novel role for RIP1 kinase in mediating TNF? production. Cell Death Dis. 2012;3:e320 pubmed publisher
    Receptor-interacting protein 1 (RIP1) is a Ser/Thr kinase with both kinase-dependent and kinase-independent roles in death receptor signaling...
  26. 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
    ..In fibroblasts, this pathway proceeds independent of RIP1 or its kinase activity, but it remains dependent on mixed lineage kinase domain-like protein (MLKL) downstream of ..
  27. Berger S, Kasparcova V, Hoffman S, Swift B, Dare L, Schaeffer M, et al. Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. J Immunol. 2014;192:5476-80 pubmed publisher
    RIP1 (RIPK1) kinase is a key regulator of TNF-induced NF-?B activation, apoptosis, and necroptosis through its kinase and scaffolding activities...
  28. Vanlangenakker N, Bertrand M, Bogaert P, Vandenabeele P, Vanden Berghe T. TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death Dis. 2011;2:e230 pubmed publisher
    ..We previously reported that cellular inhibitor of apoptosis protein-mediated receptor-interacting protein 1 (RIP1) ubiquitination acts as a cytoprotective mechanism, whereas knockdown of cylindromatosis, a RIP1-deubiquitinating ..
  29. 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
    The pronecrotic kinase, receptor 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...
  30. 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 ..
  31. Rebsamen M, Heinz L, Meylan E, Michallet M, Schroder K, Hofmann K, et al. DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep. 2009;10:916-22 pubmed publisher that these domains relay DAI-induced NF-kappaB signals through the recruitment of the RHIM-containing kinases RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI-induced NF-kappaB activation...
  32. LaRocca T, Sosunov S, Shakerley N, Ten V, Ratner A. Hyperglycemic Conditions Prime Cells for RIP1-dependent Necroptosis. J Biol Chem. 2016;291:13753-61 pubmed publisher
    Necroptosis is a RIP1-dependent programmed cell death (PCD) pathway that is distinct from apoptosis...
  33. Filliol A, Piquet Pellorce C, Raguénès Nicol C, Dion S, Farooq M, Lucas Clerc C, et al. RIPK1 protects hepatocytes from Kupffer cells-mediated TNF-induced apoptosis in mouse models of PAMP-induced hepatitis. J Hepatol. 2017;66:1205-1213 pubmed publisher
    ..In this study, we investigated the role of the receptor interacting protein kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-..
  34. Liu Y, Fan C, Zhang Y, Yu X, Wu X, Zhang X, et al. RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice. Cell Death Differ. 2017;24:1459-1469 pubmed publisher
    b>RIP1 is an essential regulator of TNF-induced signaling complexes mediating NF-?B activation, apoptosis and necroptosis...
  35. Hur G, Lewis J, Yang Q, Lin Y, Nakano H, Nedospasov S, et al. The death domain kinase RIP has an essential role in DNA damage-induced NF-kappa B activation. Genes Dev. 2003;17:873-82 pubmed
    ..Here we report that the receptor interacting protein, RIP, is the IKK upstream component, essential for the activation of NF-kappaB by DNA damage...
  36. Hofmann K. The modular nature of apoptotic signaling proteins. Cell Mol Life Sci. 1999;55:1113-28 pubmed
  37. Kang S, Fernandes Alnemri T, Rogers C, Mayes L, Wang Y, Dillon C, et al. Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3. Nat Commun. 2015;6:7515 pubmed publisher
    ..that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways...
  38. Dondelinger Y, Jouan Lanhouet S, Divert T, Theatre E, Bertin J, Gough P, et al. NF-κB-Independent Role of IKKα/IKKβ in Preventing RIPK1 Kinase-Dependent Apoptotic and Necroptotic Cell Death during TNF Signaling. Mol Cell. 2015;60:63-76 pubmed publisher
    TNF is a master pro-inflammatory cytokine. Activation of TNFR1 by TNF can result in both RIPK1-independent apoptosis and RIPK1 kinase-dependent apoptosis or necroptosis...
  39. Geng J, Ito Y, Shi L, Amin P, Chu J, Ouchida A, et al. Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis. Nat Commun. 2017;8:359 pubmed publisher
    Stimulation of TNFR1 by TNF? can promote three distinct alternative mechanisms of cell death: necroptosis, RIPK1-independent and -dependent apoptosis. How cells decide which way to die is unclear...
  40. Yang S, Wang B, Tang L, Siednienko J, Callanan J, Moynagh P. Pellino3 targets RIP1 and regulates the pro-apoptotic effects of TNF-?. Nat Commun. 2013;4:2583 pubmed publisher
    ..We show that Pellino3 targets RIP1, in a TNF-dependent manner, to inhibit TNF-induced complex II formation and caspase 8-mediated cleavage of RIP1 in ..
  41. Eliopoulos A, Das S, Tsichlis P. The tyrosine kinase Syk regulates TPL2 activation signals. J Biol Chem. 2006;281:1371-80 pubmed
    ..stimulates the JNK, ERK, and p38 mitogen-activated protein kinases and the NF-kappaB pathway by recruiting RIP1 and TRAF2 to the TNF receptor 1...
  42. Lule S, Wu L, McAllister L, Edmiston W, Chung J, Levy E, et al. Genetic Inhibition of Receptor Interacting Protein Kinase-1 Reduces Cell Death and Improves Functional Outcome After Intracerebral Hemorrhage in Mice. Stroke. 2017;48:2549-2556 pubmed publisher
    Recent studies using cultured cells and rodent intracerebral hemorrhage (ICH) models have implicated RIPK1 (receptor interacting protein kinase-1) as a driver of programmed necrosis and secondary injury based on use of chemical ..
  43. Lin Y, Choksi S, Shen H, Yang Q, Hur G, Kim Y, et al. Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J Biol Chem. 2004;279:10822-8 pubmed
    ..cells and found that tumor necrosis factor receptor (TNFR) I mediates TNF-induced necrotic cell death, and that RIP, FADD, and TRAF2 are critical components of the signaling cascade of this TNF-induced necrotic cell death...
  44. Schlicher L, Wissler M, Preiss F, Brauns Schubert P, Jakob C, Dumit V, et al. SPATA2 promotes CYLD activity and regulates TNF-induced NF-?B signaling and cell death. EMBO Rep. 2016;17:1485-1497 pubmed
    ..Thus, this study identifies SPATA2 as an important factor in the TNF signaling pathway with a substantial role for the effects mediated by the cytokine. ..
  45. Shembade N, Pujari R, Harhaj N, Abbott D, Harhaj E. The kinase IKK? inhibits activation of the transcription factor NF-?B by phosphorylating the regulatory molecule TAX1BP1. Nat Immunol. 2011;12:834-43 pubmed publisher
    ..IKK? therefore serves a key role in the negative feedback of NF-?B canonical signaling by orchestrating assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation. ..
  46. Nie D, Zhang D, Dai J, Zhang M, Zhao X, Xu W, et al. Nicotine Induced Murine Spermatozoa Apoptosis via Up-Regulation of Deubiquitinated RIP1 by Trim27 Promoter Hypomethylation. Biol Reprod. 2016;94:31 pubmed publisher
    ..The TNF pathway was further studied at the gene and protein levels. The results showed that RIP1, the key component in the TNF apoptotic pathway, was up-expressed in its deubiquitinated form in nicotine-treated ..
  47. Xu L, Li L, Shu H. TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. J Biol Chem. 2004;279:17278-82 pubmed
    ..Our studies identified a novel TRAF family member that is involved in MEKK3 signaling and apoptosis. ..
  48. 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
    ..b>RIPK1 is implicated in inflammatory and cell death signalling and its kinase activity is believed to drive RIPK3-..
  49. 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...
  50. Zheng H, Chen J, Sha S. Receptor-interacting protein kinases modulate noise-induced sensory hair cell death. Cell Death Dis. 2014;5:e1262 pubmed publisher
    ..b>RIP1 and RIP3 protein levels increased and caspase-8 was activated...
  51. Hänggi K, Vasilikos L, Valls A, Yerbes R, Knop J, Spilgies L, et al. RIPK1/RIPK3 promotes vascular permeability to allow tumor cell extravasation independent of its necroptotic function. Cell Death Dis. 2017;8:e2588 pubmed publisher
    Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 1, 3 (RIPK1, RIPK3) and mixed lineage kinase domain-like protein (MLKL)...
  52. Oerlemans M, Liu J, Arslan F, Den Ouden K, Van Middelaar B, Doevendans P, et al. Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo. Basic Res Cardiol. 2012;107:270 pubmed publisher
    ..Necrostatin-1 (Nec-1), a small molecule capable of inhibiting a key regulator of programmed necrosis (RIP1), was shown to prevent necrotic cell death in experimental models including cardiac ischemia...
  53. Duong B, Onizawa M, Oses Prieto J, Advincula R, Burlingame A, Malynn B, et al. A20 restricts ubiquitination of pro-interleukin-1β protein complexes and suppresses NLRP3 inflammasome activity. Immunity. 2015;42:55-67 pubmed publisher
    ..Pro-IL-1β also co-immunoprecipitates with RIPK1, RIPK3, caspase-1, and caspase-8 in a complex that is modified with K63-linked and unanchored polyubiquitin...
  54. Kamarajan P, Bunek J, Lin Y, Nunez G, Kapila Y. Receptor-interacting protein shuttles between cell death and survival signaling pathways. Mol Biol Cell. 2010;21:481-8 pubmed publisher
    ..matrix contacts-activates a CD95/Fas-mediated signaling pathway regulated by receptor-interacting protein (RIP), a kinase that shuttles between CD95/Fas-mediated cell death and integrin/focal adhesion kinase (FAK)-mediated ..
  55. Lin J, Kumari S, Kim C, Van T, Wachsmuth L, Polykratis A, et al. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature. 2016;540:124-128 pubmed publisher
    Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions...
  56. Chavez Valdez R, Martin L, Flock D, Northington F. Necrostatin-1 attenuates mitochondrial dysfunction in neurons and astrocytes following neonatal hypoxia-ischemia. Neuroscience. 2012;219:192-203 pubmed publisher
    Receptor interacting protein (RIP)-1 kinase activity mediates a novel pathway that signals for regulated necrosis, a form of cell death prominent in traumatic and ischemic brain injury...
  57. Suzuki T, Kikuguchi C, Sharma S, Sasaki T, Tokumasu M, Adachi S, et al. CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins. Sci Rep. 2015;5:14779 pubmed publisher
    ..reveals that mRNAs encoding cell death-related proteins, including receptor-interacting protein kinase 1 (RIPK1) and RIPK3, are stabilized in CNOT3-depleted MEFs...
  58. Hamilton A, Basic V, Andersson S, Abrink M, Ringvall M. Loss of Serglycin Promotes Primary Tumor Growth and Vessel Functionality in the RIP1-Tag2 Mouse Model for Spontaneous Insulinoma Formation. PLoS ONE. 2015;10:e0126688 pubmed publisher
    ..To further investigate the contribution of serglycin to tumor development, we have used the immunocompetent RIP1-Tag2 mouse model of spontaneous insulinoma formation crossed into serglycin deficient mice...
  59. Shutinoski B, Alturki N, Rijal D, Bertin J, Gough P, Schlossmacher M, et al. K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo. Cell Death Differ. 2016;23:1628-37 pubmed publisher
    Receptor interacting protein kinase 1 (RIPK1) participates in several cell signaling complexes that promote cell activation and cell death...
  60. Zhang Y, He W, Zhang C, Liu X, Lu Y, Wang H, et al. Role of receptor interacting protein (RIP)1 on apoptosis-inducing factor-mediated necroptosis during acetaminophen-evoked acute liver failure in mice. Toxicol Lett. 2014;225:445-53 pubmed publisher
    ..Mice were intraperitoneally injected with APAP (300 mg/kg). As expected, hepatic RIP1 was activated as early as 1 h after APAP, which is earlier than APAP-induced hepatic RIP3 upregulation...
  61. 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
    Receptor-interacting protein kinase 1 (RIPK1) represents an essential signaling node in cell death and inflammation...
  62. Cuda C, Misharin A, Gierut A, Saber R, Haines G, Hutcheson J, et al. Caspase-8 acts as a molecular rheostat to limit RIPK1- and MyD88-mediated dendritic cell activation. J Immunol. 2014;192:5548-60 pubmed publisher
    ..Uncontrolled TLR activation in a RIPK1-dependent manner is responsible for the enhanced functionality of caspase-8-deficient DCs, because deletion of the ..
  63. 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
    ..Knock-in expression of kinase inactive receptor-interacting protein kinase 1 (RIPK1) prevented hepatocyte apoptosis and HCC, while RIPK1 ablation induced TNFR1-associated death domain protein (TRADD)..
  64. Li D, Meng L, Xu T, Su Y, Liu X, Zhang Z, et al. RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system. elife. 2017;6: pubmed publisher
    A pair of kinases, RIPK1 and RIPK3, as well as the RIPK3 substrate MLKL cause a form of programmed necrotic cell death in mammals termed necroptosis...
  65. Yonekawa T, Gamez G, Kim J, Tan A, Thorburn J, Gump J, et al. RIP1 negatively regulates basal autophagic flux through TFEB to control sensitivity to apoptosis. EMBO Rep. 2015;16:700-8 pubmed publisher
    In a synthetic lethality/viability screen, we identified the serine-threonine kinase RIP1 (RIPK1) as a gene whose knockdown is highly selected against during growth in normal media, in which autophagy is not critical, but selected for in ..
  66. Polykratis A, Hermance N, Zelic M, Roderick J, Kim C, Van T, et al. Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J Immunol. 2014;193:1539-1543 pubmed publisher
    The serine/threonine kinase RIPK1 is recruited to TNFR1 to mediate proinflammatory signaling and to regulate TNF-induced cell death...
  67. McComb S, Shutinoski B, Thurston S, Cessford E, Kumar K, Sad S. Cathepsins limit macrophage necroptosis through cleavage of Rip1 kinase. J Immunol. 2014;192:5671-8 pubmed publisher
    ..results in both increased phosphorylation and decreased cleavage of receptor interacting protein kinase-1 (Rip1), leading to necroptosis that is dependent on autocrine TNF signaling...
  68. Tamura Y, Chiba Y, Tanioka T, Shimizu N, Shinozaki S, Yamada M, et al. NO donor induces Nec-1-inhibitable, but RIP1-independent, necrotic cell death in pancreatic ?-cells. FEBS Lett. 2011;585:3058-64 pubmed publisher
    ..Recently, receptor-interacting protein-1 (RIP1)-dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1, has emerged as a form of regulated ..
  69. Dowling J, Cai Y, Bertin J, Gough P, Zhang J. Kinase-independent function of RIP1, critical for mature T-cell survival and proliferation. Cell Death Dis. 2016;7:e2379 pubmed publisher
    ..b>RIP1 was originally cloned when searching for Fas-binding proteins and was later shown to associate also with the ..
  70. Melnick M, Chen H, Zhou Y, Jaskoll T. Embryonic mouse submandibular salivary gland morphogenesis and the TNF/TNF-R1 signal transduction pathway. Anat Rec. 2001;262:318-30 pubmed
    ..The results of these experiments indicate that the TNF/TNF-R1 signal transduction pathway plays an important role in balancing cell proliferation and apoptosis during SMG duct and presumptive acini formation. ..
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    Receptor-interacting protein kinase 1 (RIPK1) is an important component of the tumor necrosis factor receptor 1 (TNFR1) signaling pathway...
  72. Hur G, Kim Y, Won M, Choksi S, Liu Z. The death domain kinase RIP has an important role in DNA damage-induced, p53-independent cell death. J Biol Chem. 2006;281:25011-7 pubmed
    ..Here we report that the death domain kinase, RIP (receptor-interacting protein), is important for DNA damage-induced, p53-independent cell death...