Gene Symbol: Ripk1
Description: receptor interacting serine/threonine kinase 1
Alias: receptor-interacting serine/threonine-protein kinase 1, RIP, receptor (TNFRSF)-interacting serine-threonine kinase 1
Species: rat
Products:     Ripk1

Top Publications

  1. 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)...
  2. Zheng L, Bidere N, Staudt D, Cubre A, Orenstein J, Chan F, et al. Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Mol Cell Biol. 2006;26:3505-13 pubmed
    ..These single transducers determine cell fate by triggering NF-kappaB activation, apoptosis, and nonapoptotic death signals through separate and competing signaling pathways. ..
  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
    ..Together these data identify a role for caspase-8 in monocytes undergoing macrophagic differentiation, that is, the enzyme activated in an atypical complex down-regulates NF-kappaB activity through RIP1 cleavage. ..
  4. 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
    ..Drp1 activation caused mitochondrial fragmentation, an early and obligatory step for necrosis execution. These data defined PGAM5 as the convergent point for multiple necrosis pathways. ..
  5. 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. ..
  6. 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
    ..The differential quality of cell death mediated by the Ripoptosome may cause important pathophysiological consequences during inflammatory responses. ..
  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
    ..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)...
  8. 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
    ..In conclusion, our data indicate that cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent ROS production. ..
  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
    ..Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis. ..

More Information


  1. Feoktistova M, Geserick P, Panayotova Dimitrova D, Leverkus M. Pick your poison: the Ripoptosome, a cell death platform regulating apoptosis and necroptosis. Cell Cycle. 2012;11:460-7 pubmed publisher
    ..Our study thus supports and extends the intriguing role of the Ripoptosome for the regulation of apoptosis and necroptosis. ..
  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 ..
  3. Shi Y, Shen L, Yin C. [Expressions of receptor-interacting protein and caspase-8 in oral squamous cell carcinoma and oral precancerous lesions]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29:1802-5 pubmed
    To detect the expressions of receptor-interacting protein (RIP) and caspase-8 and investigate their roles in oral squamous cell carcinoma (OSCC) and oral precancerous lesions...
  4. 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...
  5. Xie T, Peng W, Liu Y, Yan C, Maki J, Degterev A, et al. Structural basis of RIP1 inhibition by necrostatins. Structure. 2013;21:493-9 pubmed publisher
    ..Our study provides a structural basis for RIP1 inhibition by necrostatins and offers insights into potential structure-based drug design. ..
  6. Simenc J, Lipnik Stangelj M. Staurosporine induces apoptosis and necroptosis in cultured rat astrocytes. Drug Chem Toxicol. 2012;35:399-405 pubmed publisher
    ..This report of necroptosis induced by staurosporine represents a simple approach for the in vitro induction and detection of apoptosis and necroptosis. ..
  7. 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...
  8. Chu W. Tumor necrosis factor. Cancer Lett. 2013;328:222-5 pubmed publisher
    ..Understanding new findings and emerging concepts will impact future research on the molecular mechanisms of TNF signaling in immune disorders and cancer-related inflammation. ..
  9. Vande Walle L, Wirawan E, Lamkanfi M, Festjens N, Verspurten J, Saelens X, et al. The mitochondrial serine protease HtrA2/Omi cleaves RIP1 during apoptosis of Ba/F3 cells induced by growth factor withdrawal. Cell Res. 2010;20:421-33 pubmed publisher
    ..IL-3 withdrawal causes receptor-interacting protein (RIP)1 cleavage into C-terminal fragments of 30 and 25 kDa, and only cleavage leading to the former was prevented by ..
  10. Ahmad M, Srinivasula S, Wang L, Talanian R, Litwack G, Fernandes Alnemri T, et al. CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP. Cancer Res. 1997;57:615-9 pubmed NH2-terminal caspase homology domain that interacts with caspase-2 and a COOH-terminal DD that interacts with RIP. CRADD is constitutively expressed in many tissues and thus could play a role in regulating apoptosis in mammalian ..
  11. Chen L, Zhao M, Li J, Wang Y, Bao Q, Wu S, et al. Critical role of X-box binding protein 1 in NADPH oxidase 4-triggered cardiac hypertrophy is mediated by receptor interacting protein kinase 1. Cell Cycle. 2017;16:348-359 pubmed publisher
    ..Recently, receptor interacting protein kinase 1(RIPK1) has been increasingly reported to be associated with ERS...
  12. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30:16-34 pubmed publisher
    ..In this review, we comprehensively review the recent progress in the field of PAMP recognition by PRRs and the signaling pathways activated by PRRs. ..
  13. 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
    ..Finally, we also report RIP1-independent but RIP3-mediated necroptosis in the context of TNF signaling in particular conditions. ..
  14. 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. ..
  15. Liao W, Xiao Q, Tchikov V, Fujita K, Yang W, Wincovitch S, et al. CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation. Curr Biol. 2008;18:641-9 pubmed publisher
    ..elicits cellular responses by signaling through a receptor complex that includes the essential adaptor molecule RIP. One important consequence of signaling is activation of the transcription factor NF-kappaB, and failure to ..
  16. 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
    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...
  17. de la Taille A, Chen M, Shabsigh A, Bagiella E, Kiss A, Buttyan R. Fas antigen/CD-95 upregulation and activation during castration-induced regression of the rat ventral prostate gland. Prostate. 1999;40:89-96 pubmed
    ..membrane preparations made from control or castrated rat prostates were analyzed for coprecipitation of FADD and RIP proteins to assess the activation state of the fas antigen before and after castration...
  18. Zhang H, Cheng S, Tu Y, Zhang S, Hou S, Yang Z. Protective effect of mild-induced hypothermia against moderate traumatic brain injury in rats involved in necroptotic and apoptotic pathways. Brain Inj. 2017;31:406-415 pubmed publisher moderate traumatic brain injury (TBI) rat models and the potential mechanisms, especially the involvement of RIPK1 in apoptosis and necroptosis...
  19. Cui H, Zhu Y, Jiang D. The RIP1-RIP3 Complex Mediates Osteocyte Necroptosis after Ovariectomy in Rats. PLoS ONE. 2016;11:e0150805 pubmed publisher
    ..These findings provide evidence of a potential mechanism through which osteocyte necroptosis is associated with postmenopausal osteoporosis. ..
  20. Liu J, van Mil A, Vrijsen K, Zhao J, Gao L, Metz C, et al. MicroRNA-155 prevents necrotic cell death in human cardiomyocyte progenitor cells via targeting RIP1. J Cell Mol Med. 2011;15:1474-82 pubmed publisher
    ..MiR-155 provides the opportunity to block necrosis, a conventionally thought non-regulated process, and might be a potential novel approach to improve cell engraftment for cell therapy. ..
  21. Fricker M, Vilalta A, Tolkovsky A, Brown G. Caspase inhibitors protect neurons by enabling selective necroptosis of inflamed microglia. J Biol Chem. 2013;288:9145-52 pubmed publisher
    ..Caspase-8 has both prodeath and prosurvival roles, mediating apoptosis and/or preventing RIPK1-mediated necroptosis depending on cell type and stimulus...
  22. 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
    ..In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death in rd10 mice, a mouse model of retinitis pigmentosa caused by a mutation ..
  23. 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
    The RIP kinases have emerged as essential mediators of cellular stress that integrate both extracellular stimuli emanating from various cell-surface receptors and signals coming from intracellular pattern recognition receptors...
  24. Wang J, Zhang X, Li Q, Wang K, Wang Y, Jiao J, et al. MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD. Circ Res. 2015;117:352-63 pubmed publisher
    ..of this study was to test the hypothesis that microRNA-103/107 and H19 can participate in the regulation of RIPK1- and RIPK3-dependent necrosis in fetal cardiomyocyte-derived H9c2 cells and myocardial infarction through ..
  25. Shinoda S, Skradski S, Araki T, Schindler C, Meller R, Lan J, et al. Formation of a tumour necrosis factor receptor 1 molecular scaffolding complex and activation of apoptosis signal-regulating kinase 1 during seizure-induced neuronal death. Eur J Neurosci. 2003;17:2065-76 pubmed
    ..These data suggest ASK1 may be involved in the mechanism of seizure-induced neuronal death downstream of a TNFR1 death-signalling complex. ..
  26. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45-65 pubmed
    ..In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed. ..
  27. Liu S, He X, Zhang X, Zeng F, Wang F, Zhou X. Ischemic Preconditioning-Induced SOCS-1 Protects Rat Intestinal Ischemia Reperfusion Injury via Degradation of TRAF6. Dig Dis Sci. 2017;62:105-114 pubmed publisher
    ..These data show that ischemic preconditioning may induce the activation of SOCS-1 to inhibit the TLR4-TRAF6 signaling pathway, thereby playing a protective role in ischemia-reperfusion injury. ..
  28. Zhu Y, Cui H, Gan H, Xia Y, Wang L, Wang Y, et al. Necroptosis mediated by receptor interaction protein kinase 1 and 3 aggravates chronic kidney injury of subtotal nephrectomised rats. Biochem Biophys Res Commun. 2015;461:575-81 pubmed publisher
  29. Lu B, Gong X, Wang Z, Ding Y, Wang C, Luo T, et al. Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation. Acta Pharmacol Sin. 2017;38:1543-1553 pubmed publisher
    ..These findings suggest that ROS is not only an executioner of shikonin-induced glioma cell necrosis but also a regulator of RIP1 and RIP3 expression and necrosome assembly. ..
  30. Zhang R, Zhang H, Lin Y, Li J, Pober J, Min W. RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation. J Biol Chem. 2007;282:14788-96 pubmed
    ..Our results demonstrate that RIP1-mediated AIP1 phosphorylation at the 14-3-3-binding site Ser-604 is essential for TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of ASK1-JNK/p38 apoptotic signaling. ..
  31. Ikner A, Ashkenazi A. TWEAK induces apoptosis through a death-signaling complex comprising receptor-interacting protein 1 (RIP1), Fas-associated death domain (FADD), and caspase-8. J Biol Chem. 2011;286:21546-54 pubmed publisher
    ..The proapoptotic activity of TWEAK is modulated by cIAP1 and CYLD and engages both the extrinsic and intrinsic signaling pathways. ..
  32. Temkin V, Huang Q, Liu H, Osada H, Pope R. Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis. Mol Cell Biol. 2006;26:2215-25 pubmed
    Receptor-interacting protein (RIP) has been implicated in the induction of death receptor-mediated, nonapoptotic cell death. However, the mechanisms remain to be elucidated...
  33. 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...
  34. Obitsu S, Sakata K, Teshima R, Kondo K. Eleostearic acid induces RIP1-mediated atypical apoptosis in a kinase-independent manner via ERK phosphorylation, ROS generation and mitochondrial dysfunction. Cell Death Dis. 2013;4:e674 pubmed publisher
    ..Nec1 blocked the interaction of MEK with ERK upon ESA stimulation. Together, these findings provide a new finding that ERK and kinase-independent RIP1 proteins are implicated in atypical ESA-mediated apoptosis. ..
  35. Koncz G, Hancz A, Chakrabandhu K, Gogolak P, Kerekes K, Rajnavolgyi E, et al. Vesicles released by activated T cells induce both Fas-mediated RIP-dependent apoptotic and Fas-independent nonapoptotic cell deaths. J Immunol. 2012;189:2815-23 pubmed publisher
    ..In the absence of Fas, the nonapoptotic, Fas-independent pathway could still induce cell death. In contrast to RIP-independent classical Fas-induced cell death triggered by cross-linked or membrane-bound FasL, CSup-derived stimuli-..
  36. 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
    ..These data have important implications for developing apoptosis-targeted therapies in childhood leukemia. ..
  37. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 2005;6:981-8 pubmed
    ..Knockdown' of IPS-1 by small interfering RNA blocked interferon induction by virus infection. Thus, IPS-1 is an adaptor involved in RIG-I- and Mda5-mediated antiviral immune responses. ..
  38. Shi Y, Shen L, Yin C. [Expression of caspase-8, receptor interacting protein and nuclear factor-kappaBp65 in oral lichen planus]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2010;45:11-5 pubmed
    To investigate the expressions of caspase-8, receptor interacting protein (RIP) and nuclear factor (NF)-kappaBp65 in oral lichen planus (OLP) and their relationship with cell apoptosis...
  39. Chen S, Lv X, Hu B, Shao Z, Wang B, Ma K, et al. RIPK1/RIPK3/MLKL-mediated necroptosis contributes to compression-induced rat nucleus pulposus cells death. Apoptosis. 2017;22:626-638 pubmed publisher
    ..Necroptosis-associated target molecules receptor-interacing protein kinase 1 (RIPK1), phosphorylated RIPK1 (pRIPK1), receptor-interacing protein kinase 3 (RIPK3), phosphorylated RIPK3 (pRIPK3) and ..
  40. Laukens B, Jennewein C, Schenk B, Vanlangenakker N, Schier A, Cristofanon S, et al. Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor ?-induced necroptosis. Neoplasia. 2011;13:971-9 pubmed
    ..These findings have important implications for the therapeutic exploitation of necroptosis as an alternative cell death program to overcome apoptosis resistance. ..
  41. Lotocki G, Alonso O, Dietrich W, Keane R. Tumor necrosis factor receptor 1 and its signaling intermediates are recruited to lipid rafts in the traumatized brain. J Neurosci. 2004;24:11010-6 pubmed
    ..TRADD (TNF receptor-associated death domain), TNF receptor-associated factor-2 (TRAF-2), the Ser/Thr kinase RIP (receptor-interacting protein), TRAF1, and cIAP-1 (cellular inhibitor of apoptosis protein-1), forming a survival ..