Gene Symbol: RIP
Description: receptor interacting serine/threonine kinase 1
Alias: RIP, RIP-1, RIP1, receptor-interacting serine/threonine-protein kinase 1, cell death protein RIP, receptor (TNFRSF)-interacting serine-threonine kinase 1, receptor-interacting protein 1, receptor-interacting protein kinase 1, serine/threonine-protein kinase RIP
Species: human
Products:     RIP

Top Publications

  1. Nagabhushana A, Bansal M, Swarup G. Optineurin is required for CYLD-dependent inhibition of TNF?-induced NF-?B activation. PLoS ONE. 2011;6:e17477 pubmed publisher
    ..It competes with NEMO (NF-?B essential modulator) for binding to ubiquitinated RIP (receptor interacting protein) to prevent NF-?B activation...
  2. Lin Y, Devin A, Rodriguez Y, Liu Z. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 1999;13:2514-26 pubmed
    ..We report here that the death domain kinase RIP, a key component of the TNF signaling complex, was cleaved by Caspase-8 in TNF-induced apoptosis...
  3. Lewis J, Devin A, Miller A, Lin Y, Rodriguez Y, Neckers L, et al. Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation. J Biol Chem. 2000;275:10519-26 pubmed
    The death domain kinase, receptor interacting protein (RIP), is one of the major components of the tumor necrosis factor receptor 1 (TNFR1) complex and plays an essential role in tumor necrosis factor (TNF)-mediated nuclear factor kappaB ..
  4. Bertrand M, Lippens S, Staes A, Gilbert B, Roelandt R, De Medts J, et al. cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4). PLoS ONE. 2011;6:e22356 pubmed publisher
    ..Recent studies on RIP1 and RIP2 have highlighted the importance of ubiquitination as a key process regulating their capacity to activate ..
  5. 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...
  6. 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)...
  7. Zhang S, Kovalenko A, Cantarella G, Wallach D. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity. 2000;12:301-11 pubmed
    The adapter protein RIP plays a crucial role in NF-kappaB activation by TNF...
  8. Knox P, Davies C, Ioannou M, Eliopoulos A. The death domain kinase RIP1 links the immunoregulatory CD40 receptor to apoptotic signaling in carcinomas. J Cell Biol. 2011;192:391-9 pubmed publisher
    ..We demonstrate that receptor-interacting protein 1 (RIP1) is an integral component of this complex and is required for CD40 ligand-induced caspase-8 activation and tumor ..
  9. Alvarez S, Harikumar K, Hait N, Allegood J, STRUB G, Kim E, et al. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature. 2010;465:1084-8 pubmed publisher
    ..Genetic evidence indicates that TRAF2 is necessary for the polyubiquitination of receptor interacting protein 1 (RIP1) that then serves as a platform for recruitment and stimulation of IkappaB kinase, leading to ..

More Information


  1. Thapa R, Basagoudanavar S, Nogusa S, Irrinki K, Mallilankaraman K, Slifker M, et al. NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis. Mol Cell Biol. 2011;31:2934-46 pubmed publisher
    ..Here, we show that IFN-? induces RIP1 kinase-dependent necroptosis in mammalian cells deficient in NF-?B signaling...
  2. Tian Y, Zhang Y, Zhong B, Wang Y, Diao F, Wang R, et al. RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation. J Biol Chem. 2007;282:16776-82 pubmed
    ..Taken together, our findings suggest that RBCK1 is involved in negative regulation of inflammatory signaling triggered by TNF and IL-1 through targeting TAB2/3 for degradation. ..
  3. Rébé C, Cathelin S, Launay S, Filomenko R, Prevotat L, L Ollivier C, et al. Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation. Blood. 2007;109:1442-50 pubmed
    ..the adaptor protein Fas-associated death domain (FADD), the serine/threonine kinase receptor-interacting protein 1 (RIP1) and the long isoform of FLICE-inhibitory protein FLIP...
  4. Janssens S, Tinel A, Lippens S, Tschopp J. PIDD mediates NF-kappaB activation in response to DNA damage. Cell. 2005;123:1079-92 pubmed
    ..Upon genotoxic stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappaB-activating kinase complex, NEMO, is formed...
  5. Yang Y, Xia F, Hermance N, Mabb A, Simonson S, Morrissey S, et al. A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. Mol Cell Biol. 2011;31:2774-86 pubmed publisher
    ..b>RIP1 has been implicated in this response and found to be modified in cells with damaged DNA; however, the nature of the ..
  6. Morgan M, Kim Y, Liu Z. Membrane-bound Fas ligand requires RIP1 for efficient activation of caspase-8 within the death-inducing signaling complex. J Immunol. 2009;183:3278-84 pubmed publisher
    The serine-threonine kinase RIP1 was originally identified through its ability to bind to the death domain of Fas (CD95)...
  7. Hsu H, Xiong J, Goeddel D. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell. 1995;81:495-504 pubmed
    ..However, NF-kappa B activation by TRADD is not inhibited by crmA expression, demonstrating that the signaling pathways for TNF-induced cell death and NF-kappa B activation are distinct. ..
  8. Legarda Addison D, Hase H, O Donnell M, Ting A. NEMO/IKKgamma regulates an early NF-kappaB-independent cell-death checkpoint during TNF signaling. Cell Death Differ. 2009;16:1279-88 pubmed publisher
    ..NEMO prevents receptor interacting protein-1 (RIP1) from engaging CASPASE-8 before NF-kappaB-mediated induction of antiapoptotic genes...
  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
    ..The programmed 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...
  10. Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, et al. Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death. J Biol Chem. 2001;276:36530-4 pubmed
    ..Collectively, these results indicate that both TRAF2 and TRAF5 are involved in TNF-induced NF-kappaB activation and protection from cell death. ..
  11. Enesa K, Zakkar M, Chaudhury H, Luong L, Rawlinson L, Mason J, et al. NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J Biol Chem. 2008;283:7036-45 pubmed publisher
    ..demonstrate that Cezanne can be recruited to activated TNFRs where it suppresses the build-up of polyubiquitinated RIP1 signal adapter proteins...
  12. Blankenship J, Varfolomeev E, Goncharov T, Fedorova A, Kirkpatrick D, Izrael Tomasevic A, et al. Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1). Biochem J. 2009;417:149-60 pubmed publisher
    ..These results suggest that ubiquitin binding may be an important mechanism for rapid turnover of auto-ubiquitinated c-IAP1 and c-IAP2. ..
  13. Bellail A, Olson J, Yang X, Chen Z, Hao C. A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma. Cancer Discov. 2012;2:140-55 pubmed publisher
  14. O Donnell M, Hase H, Legarda D, Ting A. NEMO inhibits programmed necrosis in an NF?B-independent manner by restraining RIP1. PLoS ONE. 2012;7:e41238 pubmed publisher
    ..genes that are required to orchestrate cell death by programmed necrosis have been identified, such as the kinase RIP1, but very little is known about the inhibitory signals that keep this necrotic cell death pathway in check...
  15. Damgaard R, Nachbur U, Yabal M, Wong W, Fiil B, Kastirr M, et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012;46:746-58 pubmed publisher
    ..We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis. ..
  16. Sun X, Lee J, Navas T, Baldwin D, Stewart T, Dixit V. RIP3, a novel apoptosis-inducing kinase. J Biol Chem. 1999;274:16871-5 pubmed
    ..gene product containing a N-terminal kinase domain that shares extensive homology with the corresponding domain in RIP (receptor-interacting protein) and RIP2...
  17. Fitzgerald K, McWhirter S, Faia K, Rowe D, Latz E, Golenbock D, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol. 2003;4:491-6 pubmed
    ..Thus, IKKepsilon and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response. ..
  18. Lucas P, Yonezumi M, Inohara N, McAllister Lucas L, Abazeed M, Chen F, et al. Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem. 2001;276:19012-9 pubmed
    ..We propose a model whereby both the Bcl10.MALT1 complex and the API2-MALT1 fusion protein activate a common downstream signaling pathway that originates with the oligomerization-dependent activation of the MALT1 caspase-like domain. ..
  19. 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...
  20. Li H, Kobayashi M, Blonska M, You Y, Lin X. Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J Biol Chem. 2006;281:13636-43 pubmed
    ..of cells with tumor necrosis factor (TNFalpha) triggers a recruitment of various signaling molecules, such as RIP, to the TNFalpha receptor 1 complex, leading to activation of NF-kappaB...
  21. 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. ..
  22. Sanz L, Sanchez P, Lallena M, Diaz Meco M, Moscat J. The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999;18:3044-53 pubmed
    ..Here we show that the previously described aPKC-binding protein, p62, selectively interacts with RIP but not with TRAF2 in vitro and in vivo. p62 bridges the aPKCs to RIP, whereas the aPKCs link IKKbeta to p62...
  23. 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, ..
  24. Bertrand M, Milutinovic S, Dickson K, Ho W, Boudreault A, Durkin J, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689-700 pubmed publisher
    ..cancer cell survival by functioning as E3 ubiquitin ligases that maintain constitutive ubiquitination of the RIP1 adaptor protein...
  25. Upton J, Kaiser W, Mocarski E. Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe. 2010;7:302-13 pubmed publisher
    ..and RHIM-dependent interactions control virus-associated necrosis, virus-induced death proceeds independently of RIP1 and is therefore distinct from TNFalpha-dependent necroptosis...
  26. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol. 2004;5:503-7 pubmed
    ..In the absence of RIP1, TLR3-mediated signals activating NF-kappa B, but not the kinase JNK or interferon-beta, were abolished, suggesting ..
  27. Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell. 2008;133:693-703 pubmed publisher
    ..These findings revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP. ..
  28. Vince J, Pantaki D, Feltham R, Mace P, Cordier S, Schmukle A, et al. TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. J Biol Chem. 2009;284:35906-15 pubmed publisher
    ..These results show that TRAF2 has anti-apoptotic signaling roles in addition to promoting NF-kappaB signaling and that efficient activation of NF-kappaB by TNFR1 requires the recruitment of cIAP1/2 by TRAF2. ..
  29. Upton J, Kaiser W, Mocarski E. Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif (RHIM)-dependent interaction with RIP1. J Biol Chem. 2008;283:16966-70 pubmed publisher
    ..Cell death suppression by M45 requires RIP homotypic interaction motif-dependent interaction with RIP1. This interaction also underlies the cell tropism role of M45 in preventing premature death of endothelial cells ..
  30. Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, et al. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol. 2012;13:1178-86 pubmed publisher
    ..These data suggest that LUBAC regulates NF-?B-dependent IL-1? responses differently in different cell types. ..
  31. Biton S, Ashkenazi A. NEMO and RIP1 control cell fate in response to extensive DNA damage via TNF-? feedforward signaling. Cell. 2011;145:92-103 pubmed publisher
    ..and NEMO/IKK-?: The first phase induced TNF-?-TNFR1 feedforward signaling, promoting the second phase and driving RIP1 phosphorylation...
  32. Sun X, Yin J, Starovasnik M, Fairbrother W, Dixit V. Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J Biol Chem. 2002;277:9505-11 pubmed
    Receptor-interacting protein (RIP), a Ser/Thr kinase component of the tumor necrosis factor (TNF) receptor-1 signaling complex, mediates activation of the nuclear factor kappaB (NF-kappaB) pathway...
  33. 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 ..
  34. Keusekotten K, Elliott P, Glockner L, Fiil B, Damgaard R, Kulathu Y, et al. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell. 2013;153:1312-26 pubmed publisher
    ..We show that OTULIN binds LUBAC and that overexpression of OTULIN prevents TNF?-induced NEMO association with ubiquitinated RIPK1. Our data suggest that OTULIN regulates Met1-polyUb signaling. ..
  35. Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T. The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal. 2010;3:re4 pubmed publisher
    ..The kinases receptor-interacting protein 1 (RIP1) and RIP3 are key signaling molecules in necrosis and are regulated by caspases and ubiquitination...
  36. Cheung H, Mahoney D, LaCasse E, Korneluk R. Down-regulation of c-FLIP Enhances death of cancer cells by smac mimetic compound. Cancer Res. 2009;69:7729-38 pubmed publisher
    ..the majority of cell lines resistant to combinations of SMC-AEG40730 and death ligands expressed caspase-8, FADD, RIP1, and ligand receptors necessary for apoptosis execution...
  37. Zhu G, Wu C, Zhao Y, Ashwell J. Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP. Curr Biol. 2007;17:1438-43 pubmed
    ..K)63-linked but not K48-linked polyubiquitin (polyUb) chains, and the ability of NEMO to bind to K63-linked polyUb RIP (receptor-interacting protein) is necessary for efficient tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB ..
  38. Hsu H, Huang J, Shu H, Baichwal V, Goeddel D. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity. 1996;4:387-96 pubmed
    ..Here, we show that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen...
  39. Chan F, Shisler J, Bixby J, Felices M, Zheng L, Appel M, et al. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J Biol Chem. 2003;278:51613-21 pubmed
    ..Because distinct molecular components including the serine/threonine protein kinase receptor-interacting protein (RIP) are required, we have referred to this alternative form of cell death as "programmed necrosis...
  40. 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...
  41. Li J, McQuade T, Siemer A, Napetschnig J, Moriwaki K, Hsiao Y, et al. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell. 2012;150:339-50 pubmed publisher
    b>RIP1 and RIP3 kinases are central players in TNF-induced programmed necrosis. Here, we report that the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures...
  42. Cusson Hermance N, Khurana S, Lee T, Fitzgerald K, Kelliher M. Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem. 2005;280:36560-6 pubmed
    b>Rip1 is required for IkappaB kinase activation in response to tumor necrosis factor alpha (TNF-alpha) and has been implicated in the Toll-like receptor 3 (TLR3) response to double-stranded RNA...
  43. Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000;1:489-95 pubmed
    ..absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP)...
  44. Yu P, Huang B, Shen M, Quast J, Chan E, Xu X, et al. Identification of RIP3, a RIP-like kinase that activates apoptosis and NFkappaB. Curr Biol. 1999;9:539-42 pubmed
    ..tumor necrosis factor receptor 1 (TNFR1) and the Fas receptor recruit complexes formed by the interactions between RIP kinase, TRADD, FADD and RAIDD - adaptor proteins that contain death domains - which in turn recruit other proteins ..
  45. Mahul Mellier A, Pazarentzos E, Datler C, Iwasawa R, Abuali G, Lin B, et al. De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell Death Differ. 2012;19:891-9 pubmed publisher
    ..complex that is recruited upon ligand binding and controls the signalling activity of the TNFR1-interacting protein RIP1 by removing its K63-linked ubiquitin chains...
  46. 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...
  47. Dynek J, Goncharov T, Dueber E, Fedorova A, Izrael Tomasevic A, Phu L, et al. c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 2010;29:4198-209 pubmed publisher
    ..demonstrate that c-IAP1 and UbcH5 family promote K11-linked polyubiquitination of receptor-interacting protein 1 (RIP1) in vitro and in vivo...
  48. 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...
  49. Kaiser W, Offermann M. Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J Immunol. 2005;174:4942-52 pubmed
    ..TRIF physically interacted with the RHIM-containing proteins RIP1 and RIP3, and deletion and mutational analyses revealed that the RHIM in TRIF was essential for TRIF-induced ..
  50. Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, Wallberg F, et al. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell. 2011;43:432-48 pubmed publisher
    ..quot; It contains the core components RIP1, FADD, and caspase-8, and assembles in response to genotoxic stress-induced depletion of XIAP, cIAP1 and cIAP2...
  51. Wagner S, Carpentier I, Rogov V, Kreike M, Ikeda F, Lohr F, et al. Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins. Oncogene. 2008;27:3739-45 pubmed publisher
    ..Taken together, these data illustrate an important role for ubiquitin binding in the negative regulation of NF-kappaB signaling by ABINs and identify UBAN as a novel UBD. ..
  52. Rajput A, Kovalenko A, Bogdanov K, Yang S, Kang T, Kim J, et al. RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein. Immunity. 2011;34:340-51 pubmed publisher
    ..transcription factor IRF3 by the ribonucleic acid sensor RIG-I was restricted by caspase-8-mediated cleavage of the RIP1 protein, which resulted in conversion of RIP1 from a signaling enhancer to a signaling inhibitor...
  53. 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
    ..These findings implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3. ..
  54. Kim S, Ohoka N, Okuhira K, Sai K, Nishimaki Mogami T, Naito M. Modulation of RIP1 ubiquitylation and distribution by MeBS to sensitize cancer cells to tumor necrosis factor ?-induced apoptosis. Cancer Sci. 2010;101:2425-9 pubmed publisher
    ..Here, we show that ubiquitylation and distribution of RIP1, a protein ubiquitylated by cIAP1, is modulated by MeBS...
  55. 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...
  56. Oshima S, Turer E, Callahan J, Chai S, Advincula R, Barrera J, et al. ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development. Nature. 2009;457:906-9 pubmed publisher
    ..These studies provide insights into how ubiquitination and ubiquitin sensing proteins regulate cellular and organismal survival. ..
  57. Newton K, Matsumoto M, Wertz I, Kirkpatrick D, Lill J, Tan J, et al. Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. Cell. 2008;134:668-78 pubmed publisher
    ..We use these antibodies to demonstrate that RIP1, which is essential for tumor necrosis factor-induced NF-kappaB activation, and IRAK1, which participates in ..
  58. Varfolomeev E, Goncharov T, Fedorova A, Dynek J, Zobel K, Deshayes K, et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem. 2008;283:24295-9 pubmed publisher
    ..of c-IAP1 or cells where the c-IAP proteins were eliminated using IAP antagonists, we show that TNFalpha-induced RIP1 ubiquitination is abrogated in the absence of c-IAPs...
  59. Ea C, Deng L, Xia Z, Pineda G, Chen Z. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006;22:245-57 pubmed
    The receptor interacting protein kinase 1 (RIP1) is essential for the activation of nuclear factor kappaB (NF-kappaB) by tumor necrosis factor alpha (TNFalpha)...
  60. Wertz I, O Rourke K, Zhou H, Eby M, Aravind L, Seshagiri S, et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004;430:694-9 pubmed
    ..the OTU (ovarian tumour) family, removes lysine-63 (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex...
  61. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114:181-90 pubmed
    ..The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B...
  62. Xu M, Skaug B, Zeng W, Chen Z. A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta. Mol Cell. 2009;36:302-14 pubmed publisher
    ..that IKK activation by TNFalpha requires Ubc5, which functions with the E3 cIAP1 to catalyze polyubiquitination of RIP1 not restricted to K63 of ubiquitin...
  63. Kanayama A, Seth R, Sun L, Ea C, Hong M, Shaito A, et al. TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell. 2004;15:535-48 pubmed
    ..We also show that TAB2 binds to polyubiquitinated RIP following TNFalpha stimulation...
  64. 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...
  65. Duprez L, Bertrand M, Vanden Berghe T, Dondelinger Y, Festjens N, Vandenabeele P. Intermediate domain of receptor-interacting protein kinase 1 (RIPK1) determines switch between necroptosis and RIPK1 kinase-dependent apoptosis. J Biol Chem. 2012;287:14863-72 pubmed publisher
  66. Inohara N, Koseki T, Lin J, del Peso L, Lucas P, Chen F, et al. An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways. J Biol Chem. 2000;275:27823-31 pubmed
    ..Similarly, the RICK-related kinase RIP associated via its intermediate region with IKKgamma...
  67. Huang C, Luo Y, Zhao J, Yang F, Zhao H, Fan W, et al. Shikonin kills glioma cells through necroptosis mediated by RIP-1. PLoS ONE. 2013;8:e66326 pubmed publisher
    ..Shikonin was reported to induce necroptosis in leukemia cells, but apoptosis in glioma cell lines. Thus, it is needed to clarify whether shikonin could cause necroptosis in glioma cells and investigate its underlying mechanisms...
  68. Chen D, Li X, Zhai Z, Shu H. A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-kappa B activation. J Biol Chem. 2002;277:15985-91 pubmed
    Receptor-interacting protein (RIP) is a serine/threonine protein kinase that is critically involved in tumor necrosis factor receptor-1 (TNF-R1)-induced NF-kappa B activation...
  69. Zhang N, Chen Y, Jiang R, Li E, Chen X, Xi Z, et al. PARP and RIP 1 are required for autophagy induced by 11'-deoxyverticillin A, which precedes caspase-dependent apoptosis. Autophagy. 2011;7:598-612 pubmed
    ..of LC3-II and the cleavage of caspase 3, which was confirmed by depletion of receptor-interacting protein 1 (RIP-1), a crucial necrostatin-1-targeted adaptor kinase mediating cell death and survival...
  70. 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)...
  71. 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...
  72. Shembade N, Harhaj N, Parvatiyar K, Copeland N, Jenkins N, Matesic L, et al. The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nat Immunol. 2008;9:254-62 pubmed publisher
    ..however, little is known about the mechanisms of A20-mediated inactivation of signaling intermediates such as RIP1. Here we demonstrate that the regulatory molecule TAX1BP1 recruited the E3 ligase Itch to A20 via two 'PPXY' motifs...
  73. 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. ..
  74. Löder S, Fakler M, Schoeneberger H, Cristofanon S, Leibacher J, Vanlangenakker N, et al. RIP1 is required for IAP inhibitor-mediated sensitization of childhood acute leukemia cells to chemotherapy-induced apoptosis. Leukemia. 2012;26:1020-9 pubmed publisher
    ..Importantly, we identify RIP1 as a critical regulator of this synergism of IAP inhibitors and AraC that mediates the formation of a RIP1/FADD/..
  75. Feoktistova M, Geserick P, Kellert B, Dimitrova D, Langlais C, Hupe M, et al. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol Cell. 2011;43:449-63 pubmed publisher
    ..It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms...
  76. Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, et al. Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis. Proc Natl Acad Sci U S A. 1999;96:1042-7 pubmed
    ..7K can partially reverse apoptotic death induced by FIP-3. FIP-3 also was shown to bind to other cell proteins, RIP and NIK, which previously had been described as essential components of TNF-alpha-induced NF-kappaB activation...