Gene Symbol: RIP3
Description: receptor interacting serine/threonine kinase 3
Alias: RIP3, receptor-interacting serine/threonine-protein kinase 3, RIP-3, RIP-like protein kinase 3, receptor interacting protein 3
Species: human
Products:     RIP3

Top Publications

  1. 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
    ..We isolated a kinase, RIP3, which shares homology with the kinase domain of RIP and RIP2 (also known as Rick or CARDIAK)...
  2. 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...
  3. 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...
  4. 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...
  5. Kasof G, Prosser J, Liu D, Lorenzi M, Gomes B. The RIP-like kinase, RIP3, induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria. FEBS Lett. 2000;473:285-91 pubmed
    A RIP-like protein, RIP3, has recently been reported that contains an N-terminal kinase domain and a novel C-terminal domain that promotes apoptosis. These experiments further characterize RIP3-mediated apoptosis and NF-kappaB activation...
  6. 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
    ..Trif recruited the kinases receptor interacting protein (RIP)-1 and RIP3 through its RIP homotypic interaction motif...
  7. 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 apoptosis and ..
  8. 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...
  9. 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
    ..quot;rheostat" that is controlled by cFLIP isoforms in the Ripoptosome and decides if cell death occurs by RIP3-dependent necroptosis or caspase-dependent apoptosis. RIP1 is the core component of the complex...

More Information

Publications121 found, 100 shown here

  1. 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...
  2. 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
    b>RIP3 is a novel gene product containing a N-terminal kinase domain that shares extensive homology with the corresponding domain in RIP (receptor-interacting protein) and RIP2...
  3. 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...
  4. 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...
  5. 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)..
  6. 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...
  7. Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, Luo J, et al. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci U S A. 2012;109:5322-7 pubmed publisher
    ..It is known that receptor interacting protein (RIP) kinases, RIP1 and RIP3, are key effectors of TNF-induced necrosis, but little is known about how these two RIP kinases mediate this ..
  8. 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...
  9. Song X, Zhu S, Xie Y, Liu J, Sun L, Zeng D, et al. JTC801 Induces pH-dependent Death Specifically in Cancer Cells and Slows Growth of Tumors in Mice. Gastroenterology. 2018;154:1480-1493 pubmed publisher
    ..Levels of CA9 are increased in human cancer tissues. JTC801 might be developed for treatment of pancreatic cancer. ..
  10. Shen J, Cao S, Sun X, Pan B, Cao J, Che D, et al. Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line. Cell Physiol Biochem. 2018;51:2938-2954 pubmed publisher
    ..was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in ..
  11. Xie Y, Zhu S, Zhong M, Yang M, Sun X, Liu J, et al. Inhibition of Aurora Kinase A Induces Necroptosis in Pancreatic Carcinoma. Gastroenterology. 2017;153:1429-1443.e5 pubmed publisher
    ..CCT137690 slowed growth of orthotopic tumors from PDAC cells in mice, and expression of AURKA and GSK3β associate with patient survival times. AURKA might be targeted for treatment of pancreatic cancer. ..
  12. González Juarbe N, Gilley R, Hinojosa C, Bradley K, Kamei A, Gao G, et al. Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia. PLoS Pathog. 2015;11:e1005337 pubmed publisher
    Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL...
  13. Pearson J, Giogha C, Mühlen S, Nachbur U, Pham C, Zhang Y, et al. EspL is a bacterial cysteine protease effector that cleaves RHIM proteins to block necroptosis and inflammation. Nat Microbiol. 2017;2:16258 pubmed publisher
  14. Yang B, Lan S, Dieudé M, Sabo Vatasescu J, Karakeussian Rimbaud A, Turgeon J, et al. Caspase-3 Is a Pivotal Regulator of Microvascular Rarefaction and Renal Fibrosis after Ischemia-Reperfusion Injury. J Am Soc Nephrol. 2018;29:1900-1916 pubmed publisher
    ..These findings also demonstrate the predominant role of microvascular over tubular injury as a driver of progressive renal damage and fibrosis after IRI. ..
  15. Filipczak P, Thomas C, Chen W, Salzman A, McDonald J, Lin Y, et al. TSC2 Deficiency Unmasks a Novel Necrosis Pathway That Is Suppressed by the RIP1/RIP3/MLKL Signaling Cascade. Cancer Res. 2016;76:7130-7139 pubmed
    ..Furthermore, blocking RIP1/RIP3/MLKL-dependent signaling using chemical inhibitors necrostatin-1 (Nec-1) and necrosulfonamide (NSA) synergizes with ..
  16. Abd Ellatif R, Hegab I, Atef M, Sadek M, Hafez Y. Diacerein protects against glycerol-induced acute kidney injury: Modulating oxidative stress, inflammation, apoptosis and necroptosis. Chem Biol Interact. 2019;306:47-53 pubmed publisher
    ..CONCLUSION: These results demonstrated that diacerein might have potential application in the amelioration of AKI via its anti-oxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic effects. ..
  17. Corradetti C, Jog N, Gallucci S, Madaio M, Balachandran S, Caricchio R. Immune-Mediated Nephropathy and Systemic Autoimmunity in Mice Does Not Require Receptor Interacting Protein Kinase 3 (RIPK3). PLoS ONE. 2016;11:e0163611 pubmed publisher
    ..We conclude that RIPK3 is dispensable for the pathogenesis of lupus and immune mediated nephropathy as to accelerate, worsen or ameliorate the disease. ..
  18. Ni H, Chao X, Kaseff J, Deng F, Wang S, Shi Y, et al. Receptor-Interacting Serine/Threonine Kinase 3 (RIP3)-Mixed Lineage Kinase Like Protein (MLKL)-Mediated Necroptosis Contributes to Ischemia-Reperfusion Injury of Steatotic Livers. Am J Pathol. 2019;: pubmed publisher regulated by three key proteins: receptor-interacting serine/threonine kinase 1 (RIP1; official name RIPK1), RIP3, and mixed lineage kinase like protein (MLKL)...
  19. Qu C, Yuan Z, Yu X, Huang Y, Yang G, Chen J, et al. Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism. Pharmacol Res. 2017;121:70-82 pubmed publisher
    ..signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins...
  20. Cai Q, Gan J, Luo R, Qu Y, Li S, Wan C, et al. The role of necroptosis in status epilepticus-induced brain injury in juvenile rats. Epilepsy Behav. 2017;75:134-142 pubmed publisher
    ..immunofluorescence (IF) staining were used to investigate the expression of receptor interacting protein kinase-3 (RIP3), mixed lineage kinase domain-like (MLKL), and p-MLKL after SE...
  21. Mengying Z, Yiyue X, Tong P, Yue H, Limpanont Y, Ping H, et al. Apoptosis and necroptosis of mouse hippocampal and parenchymal astrocytes, microglia and neurons caused by Angiostrongylus cantonensis infection. Parasit Vectors. 2017;10:611 pubmed publisher
    ..Compared with those of the control group, the mRNA levels of caspase-3, -4, -6, and RIP3 and the protein levels of caspase-4, cleaved caspase-3, cleaved caspase-6, RIP3, and pRIP3 were obviously elevated...
  22. Berkhout L, Barikbin R, Schiller B, Ravichandran G, Krech T, Neumann K, et al. Deletion of tumour necrosis factor α receptor 1 elicits an increased TH17 immune response in the chronically inflamed liver. Sci Rep. 2019;9:4232 pubmed publisher
    ..It instead caused enhanced infiltration of TH17 cells and CX3CR1+ monocytes into the injured tissue, which was accompanied by increased RIPK3 activation and IL-17 production. ..
  23. Chen Z, Zhong D, Li G. The role of microglia in viral encephalitis: a review. J Neuroinflammation. 2019;16:76 pubmed publisher
    ..The relationship between the two needs to be further confirmed. How to properly regulate the function of microglia and make it exert more anti-inflammatory effects is our next research direction. ..
  24. Chtourou Y, Slima A, Makni M, Gdoura R, Fetoui H. Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats. Pharmacol Rep. 2015;67:1090-7 pubmed publisher
    ..of gene expression of the tumor necrosis factor-α (TNF-α) and receptor-interacting protein kinase 3 (RIP3) mRNA that contributed to the elucidation of cholesterol-induced necroptosis, a recently described type of ..
  25. Takemura R, Takaki H, Okada S, Shime H, Akazawa T, Oshiumi H, et al. PolyI:C-Induced, TLR3/RIP3-Dependent Necroptosis Backs Up Immune Effector-Mediated Tumor Elimination In Vivo. Cancer Immunol Res. 2015;3:902-14 pubmed publisher
    ..CT26 necroptosis depended on the TLR3-TICAM-1-RIP3 axis in the tumor cells to produce reactive oxygen species, but not on MDA5, MAVS, or the caspases/inflammasome ..
  26. Wenz C, Faust D, Linz B, Turmann C, Nikolova T, Bertin J, et al. t-BuOOH induces ferroptosis in human and murine cell lines. Arch Toxicol. 2018;92:759-775 pubmed publisher
    ..We identify that t-BuOOH and H2O2 produce a different pattern of lipid peroxidation, thereby leading to different cell death pathways and present t-BuOOH as a novel inducer of ferroptosis. ..
  27. Yang M, Lv Y, Tian X, Lou J, An R, Zhang Q, et al. Neuroprotective Effect of ?-Caryophyllene on Cerebral Ischemia-Reperfusion Injury via Regulation of Necroptotic Neuronal Death and Inflammation: In Vivo and in Vitro. Front Neurosci. 2017;11:583 pubmed publisher
    ..Thus, BCP alleviates ischemic brain damage potentially by inhibiting necroptotic neuronal death and inflammatory response. This study suggests a novel application for BCP as a neuroprotective agent. ..
  28. Honarpisheh M, Desai J, Marschner J, Weidenbusch M, Lech M, Vielhauer V, et al. Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis. Biosci Rep. 2016;36: pubmed publisher
  29. Xu Y, Wang J, Song X, Wei R, He F, Peng G, et al. Protective mechanisms of CA074-me (other than cathepsin-B inhibition) against programmed necrosis induced by global cerebral ischemia/reperfusion injury in rats. Brain Res Bull. 2016;120:97-105 pubmed publisher
    ..protein 70 (Hsp70), cathepsin-B, lysosomal-associated membrane protein 1 (LAMP-1), receptor-interacting protein 3 (RIP3), and the change of lysosomal pH were evaluated respectively...
  30. Hong J, Kim S, Lee S. Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion. Toxicol Appl Pharmacol. 2016;308:1-10 pubmed publisher
    ..described cell death as "programmed necrosis" that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases...
  31. Huang Z, Zhou T, Sun X, Zheng Y, Cheng B, Li M, et al. Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation. Cell Death Differ. 2018;25:180-189 pubmed publisher
    ..We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury ..
  32. Nugues A, El Bouazzati H, Hétuin D, Berthon C, Loyens A, Bertrand E, et al. RIP3 is downregulated in human myeloid leukemia cells and modulates apoptosis and caspase-mediated p65/RelA cleavage. Cell Death Dis. 2014;5:e1384 pubmed publisher
    The receptor-interacting protein kinase 3 (RIP3) associates with RIP1 in a necrosome complex that can induce necroptosis, apoptosis, or cell proliferation...
  33. Zhang T, Zhang Y, Cui M, Jin L, Wang Y, Lv F, et al. CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med. 2016;22:175-82 pubmed publisher
    ..Here we show that receptor-interacting protein 3 (RIP3) triggers myocardial necroptosis, in addition to apoptosis and inflammation, through activation of Ca(2+)-..
  34. Murphy J, Vince J. Post-translational control of RIPK3 and MLKL mediated necroptotic cell death. F1000Res. 2015;4: pubmed publisher
    ..Finally, based on current evidence, we discuss the potential mechanisms by which the essential, and possibly terminal, necroptotic effector, MLKL, triggers the disruption of cellular membranes to cause cell lysis. ..
  35. Das A, McDonald D, Dixon Mah Y, Jacqmin D, Samant V, Vandergrift W, et al. RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma. Tumour Biol. 2016;37:7525-34 pubmed publisher
    ..When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed...
  36. Wang Z, Guo L, Zhou H, Qu H, Wang S, Liu F, et al. Using drugs to target necroptosis: dual roles in disease therapy. Histol Histopathol. 2018;33:773-789 pubmed publisher
    ..The most common accepted mechanism is through the RIP1-RIP3-MLKL axis to regulate necroptotic cell death...
  37. Guo H, Omoto S, Harris P, Finger J, Bertin J, Gough P, et al. Herpes simplex virus suppresses necroptosis in human cells. Cell Host Microbe. 2015;17:243-51 pubmed publisher
    ..necroptosis in human cells by inhibiting the interaction between receptor-interacting protein kinase 1 (RIP1) and RIP3, a key step in tumor necrosis factor (TNF)-induced necroptosis...
  38. de Almagro M, Goncharov T, Newton K, Vucic D. Cellular IAP proteins and LUBAC differentially regulate necrosome-associated RIP1 ubiquitination. Cell Death Dis. 2015;6:e1800 pubmed publisher
    ..of cell death that relies on receptor-interacting protein kinases RIP1 (receptor-interacting protein kinases 1) and RIP3. Tumor necrosis factor-α (TNFα)-stimulated assembly of the TNFR1 (TNF receptor 1)-associated signaling ..
  39. Cuda C, Misharin A, Khare S, Saber R, Tsai F, Archer A, et al. Conditional deletion of caspase-8 in macrophages alters macrophage activation in a RIPK-dependent manner. Arthritis Res Ther. 2015;17:291 pubmed publisher
    ..These data demonstrate that caspase-8 functions uniquely in macrophages by controlling the response to TLR activation and macrophage polarization in an RIPK-dependent manner. ..
  40. Yu M, Wang Q, Qi W, Zhang K, Liu J, Tao P, et al. Expression of inflammation-related genes in the lung of BALB/c mice response to H7N9 influenza A virus with different pathogenicity. Med Microbiol Immunol. 2016;205:501-9 pubmed publisher
    ..In this research, expression pattern and histological distribution of inflammation-related genes, RIP3, NLRP3, IL-1?, TNF-?, Slit2 and Robo4 in the lung of BALB/c mice infected with two H7N9 IAV strains with only a PB2 ..
  41. Zhang Y, Su S, Zhao S, Yang Z, Zhong C, Chen X, et al. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun. 2017;8:14329 pubmed publisher
    ..This specific phosphorylation then enables RIP1 to recruit RIP3 and form a functional necrosome, a central controller of necroptosis...
  42. Liu Z, Wu B, Guo Y, Zhou Y, Fu Z, Xu B, et al. Necrostatin-1 reduces intestinal inflammation and colitis-associated tumorigenesis in mice. Am J Cancer Res. 2015;5:3174-85 pubmed
    ..known as a specific inhibitor of necroptosis, through preventing the receptor-interacting protein (RIP) 1 and RIP3 interaction...
  43. Zhang Y, Cheng J, Zhang J, Wu X, Chen F, Ren X, et al. Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting cIAPs-mediated inhibition of RIP1 and RIP3 activation. Biochem Biophys Res Commun. 2016;477:761-767 pubmed publisher
    ..Further evidences demonstrated reduced levels of both RIP1 and RIP 3 upon PS-341 treatment, concomitantly, a more strong association of RIP1 with cIAPs and less with RIP3 was found ..
  44. Conos S, Chen K, De Nardo D, Hara H, Whitehead L, Núñez G, et al. Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner. Proc Natl Acad Sci U S A. 2017;114:E961-E969 pubmed publisher
    ..Collectively, these results demonstrate the potential importance of NLRP3 inflammasome activity as a driving force for inflammation in MLKL-dependent diseases. ..
  45. Wegner K, Saleh D, Degterev A. Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis. Trends Pharmacol Sci. 2017;38:202-225 pubmed publisher
    ..This review will provide an overview of the current understanding of the human disease relevance of this pathway, and potential therapeutic strategies, targeting necroptosis mediators in various pathologies. ..
  46. Bittner S, Knoll G, Ehrenschwender M. Death receptor 3 mediates necroptotic cell death. Cell Mol Life Sci. 2017;74:543-554 pubmed publisher
    ..DR3-mediated necroptosis critically depends on receptor-interacting protein 1 (RIP1) and RIP3, the core components of the necroptotic machinery, which activate the pseudo-kinase mixed lineage kinase domain-..
  47. Bhatti I, Abhari B, Fulda S. Identification of a synergistic combination of Smac mimetic and Bortezomib to trigger cell death in B-cell non-Hodgkin lymphoma cells. Cancer Lett. 2017;405:63-72 pubmed publisher
    ..Importantly, genetic silencing of key components of necroptosis signaling such as MLKL or RIP3 significantly protects DG-75 cells from BV6/Bortezomib-induced cell death in the presence and even the absence ..
  48. Zhang J, Liu Q, Shi L, Qin P, Wang Q. Honokiol triggers receptor?interacting protein kinase 3?mediated cell death of neuroblastoma cells by upregulating reactive oxygen species. Mol Med Rep. 2017;16:8525-8529 pubmed publisher
    ..which was associated with upregulation of the protein expression of receptor?interacting protein kinase 3 (RIP3), as demonstrated by western blot analysis...
  49. Zhu Y, Cui H, Xia Y, Gan H. RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats. PLoS ONE. 2016;11:e0156729 pubmed publisher
  50. Wang Z, Guo L, Wang Y, Zhou H, Wang S, Chen D, et al. Inhibition of HSP90α protects cultured neurons from oxygen-glucose deprivation induced necroptosis by decreasing RIP3 expression. J Cell Physiol. 2018;233:4864-4884 pubmed publisher
    ..Recent studies have shown that HSP90α is involved in receptor interacting protein 3 (RIP3)-mediated necroptosis in HT29 cells...
  51. Huang Y, Tsai M, Hsieh P, Shih J, Wang T, Wang Y, et al. Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. Toxicol Appl Pharmacol. 2017;329:128-139 pubmed publisher
    ..Galangin administration also reduced the expression levels of RIP1 and RIP3 to inhibit cisplatin-induced RIP1/RIP3-dependent necroptosis...
  52. Blériot C, Lecuit M. The interplay between regulated necrosis and bacterial infection. Cell Mol Life Sci. 2016;73:2369-78 pubmed publisher
    ..We present how these pathways are modulated in the context of infection by a series of model bacterial pathogens. ..
  53. Weigert M, Binks A, Dowson S, Leung E, Athineos D, Yu X, et al. RIPK3 promotes adenovirus type 5 activity. Cell Death Dis. 2017;8:3206 pubmed publisher
    ..Together, these results suggest that adenovirus induces a form of programmed necrosis that differs from classical TSZ necroptosis. ..
  54. Sun Y, Zhai L, Ma S, Zhang C, Zhao L, Li N, et al. Down-regulation of RIP3 potentiates cisplatin chemoresistance by triggering HSP90-ERK pathway mediated DNA repair in esophageal squamous cell carcinoma. Cancer Lett. 2018;418:97-108 pubmed publisher
    Receptor interacting protein kinase 3 (RIP3) is a critical regulator of programmed necrotic cell death. Here, we observed that RIP3 was significantly down-regulated in esophageal cancer...
  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. Qin S, Yang C, Huang W, Du S, Mai H, Xiao J, et al. Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia. Pharmacol Res. 2018;133:218-235 pubmed publisher
    ..Together, our results demonstrate that SFN attenuates LPS-induced pro-inflammatory responses through down-regulation of MAPK/NF-κB signaling pathway in BV-2 microglia and thus indirectly suppresses microglia-mediated neuronal damage. ..
  57. 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 ..
  58. Hojo T, Siemieniuch M, Lukasik K, Piotrowska Tomala K, Jonczyk A, Okuda K, et al. Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows. Sci Rep. 2016;6:38211 pubmed publisher
    ..Nec-1 decreased both RIPK1 and RIPK3 protein expression (P?<?0.05). These findings suggest that RIPKs-dependent necroptosis is a potent mechanism responsible for bovine structural luteolysis induced by pro-inflammatory cytokines. ..
  59. Shahsavari Z, Karami Tehrani F, Salami S. Targeting cell necroptosis and apoptosis induced by Shikonin via receptor interacting protein kinases in estrogen receptor positive breast cancer cell line, MCF-7. Anticancer Agents Med Chem. 2017;: pubmed publisher
    ..On the basis of present findings, Shikonin has been suggested as a good candidate for the induction of cell death in ER+ breast cancer, although further investigations are required...
  60. 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
    ..RIP2 and RIP3 are related kinases that share extensive sequence homology with the kinase domain of RIP...
  61. Gao R, Zhao S, Jiang X, Sun Y, Zhao S, Gao J, et al. A large-scale screen reveals genes that mediate electrotaxis in Dictyostelium discoideum. Sci Signal. 2015;8:ra50 pubmed publisher
    ..Furthermore, we found that electrotaxis was decreased in mutants lacking gefA, rasC, rip3, lst8, or pkbR1, genes that encode other components of the TORC2-PKB pathway...
  62. Davies K, Tanzer M, Griffin M, Mok Y, Young S, Qin R, et al. The brace helices of MLKL mediate interdomain communication and oligomerisation to regulate cell death by necroptosis. Cell Death Differ. 2018;25:1567-1580 pubmed publisher
    ..These findings illustrate that the brace helices play an active role in MLKL regulation, rather than simply acting as a tether between the 4HB and pseudokinase domains. ..
  63. Mihaly S, Sakamachi Y, Ninomiya Tsuji J, Morioka S. Noncanonical cell death program independent of caspase activation cascade and necroptotic modules is elicited by loss of TGFβ-activated kinase 1. Sci Rep. 2017;7:2918 pubmed publisher
    ..Therefore, loss of TAK1 elicits noncanonical cell death which is mediated by RIPK1-induced oxidative stress upon caspase and necroptosis inhibition to further ensure induction of cell death. ..
  64. Yang X, Yi T, Zhang S, Xu Z, Yu Z, Sun H, et al. Hypoxia-inducible factor-1 alpha is involved in RIP-induced necroptosis caused by in vitro and in vivo ischemic brain injury. Sci Rep. 2017;7:5818 pubmed publisher
    ..deficit, while zVAD-fmk (zVAD, an apoptotic inhibitor), GSK'872 (a receptor interacting protein kinase-3 (RIP3) inhibitor), and combined treatment alleviated cell death and ischemic brain injury...
  65. Reynoso E, Liu H, Li L, Yuan A, Chen S, Wang Z. Thioredoxin-1 actively maintains the pseudokinase MLKL in a reduced state to suppress disulfide bond-dependent MLKL polymer formation and necroptosis. J Biol Chem. 2017;292:17514-17524 pubmed publisher
    ..Our results further suggest new directions for targeted cancer therapy in which thioredoxin inhibitors like PX-12 could potentially be used to specifically target cancers expressing high levels of MLKL or MLKL short isoforms. ..
  66. Hussain M, Zimmermann V, van Wijk S, Fulda S. Mouse lung fibroblasts are highly susceptible to necroptosis in a reactive oxygen species-dependent manner. Biochem Pharmacol. 2018;153:242-247 pubmed publisher
    ..Thus, our study demonstrates for the first time that MLFs are prone to undergo necroptosis in response to a prototypic necroptotic stimulus and identifies ROS as important mediators of TSZ-triggered necroptosis. ..
  67. Yang Y, Hu W, Feng S, Ma J, Wu M. RIP3 beta and RIP3 gamma, two novel splice variants of receptor-interacting protein 3 (RIP3), downregulate RIP3-induced apoptosis. Biochem Biophys Res Commun. 2005;332:181-7 pubmed
    Receptor-interacting protein 3 (RIP3) is an apoptosis inducing member of the RIP family. Here we report two novel splice variants of human RIP3, designated RIP3 beta and RIP3 gamma respectively...
  68. Tian W, Li Y, Zhang J, Li J, Gao J. Combined analysis of DNA methylation and gene expression profiles of osteosarcoma identified several prognosis signatures. Gene. 2018;650:7-14 pubmed publisher
    ..Based on this study, some novel targets were identified for OS, which would be helpful in its early diagnosis and treatment. ..
  69. Martin Sanchez D, Fontecha Barriuso M, Carrasco S, Sanchez Niño M, Mässenhausen A, Linkermann A, et al. TWEAK and RIPK1 mediate a second wave of cell death during AKI. Proc Natl Acad Sci U S A. 2018;115:4182-4187 pubmed publisher
    ..This may be relevant for clinical AKI, since using current diagnostic criteria, severe injury had already led to loss of renal function at diagnosis. ..
  70. Yang Y, Ma J, Chen Y, Wu M. Nucleocytoplasmic shuttling of receptor-interacting protein 3 (RIP3): identification of novel nuclear export and import signals in RIP3. J Biol Chem. 2004;279:38820-9 pubmed
    Receptor-interacting protein 3 (RIP3), a member of the RIP Ser/Thr kinase family, has been characterized as a pro-apoptotic protein involved in the tumor necrosis factor receptor-1 signaling pathway...
  71. Zhao Y, Alonso C, Ballester I, Song J, Chang S, Guleng B, et al. Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. Inflamm Bowel Dis. 2012;18:603-12 pubmed publisher
    ..GEF-H1 connects tyrosine kinase function to NOD-like receptor signaling and is fundamental to the regulation of microbial recognition by ubiquitous innate immune mechanisms mediated by Rip2 kinase. ..
  72. Lee E, Kim J, Ahn Y, Seo J, Ko A, Jeong M, et al. Ubiquitination and degradation of the FADD adaptor protein regulate death receptor-mediated apoptosis and necroptosis. Nat Commun. 2012;3:978 pubmed publisher
    ..Our data reveal a novel mechanism by which fas-associated protein with death domain is regulated via an ubiquitination-induced degradation pathway. ..
  73. Yu X, Deng Q, Li W, Xiao L, Luo X, Liu X, et al. Neoalbaconol induces cell death through necroptosis by regulating RIPK-dependent autocrine TNFα and ROS production. Oncotarget. 2015;6:1995-2008 pubmed
    ..Taken together, these results suggested that two distinct mechanisms are involved in NA-induced necroptosis and include RIPK1/NF-κB-dependent expression of TNFα and RIPK3-dependent generation of ROS. ..
  74. 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
    Necroptosis is a type of programmed necrosis regulated by receptor interacting protein kinase 1 (RIP1) and RIP3. Necroptosis is found to be accompanied by an overproduction of reactive oxygen species (ROS), but the role of ROS in ..
  75. Yang H, Fu Y, Liu X, Shahi P, Mavlyutov T, Li J, et al. Role of the sigma-1 receptor chaperone in rod and cone photoreceptor degenerations in a mouse model of retinitis pigmentosa. Mol Neurodegener. 2017;12:68 pubmed publisher
    ..The receptor-interacting protein kinases (RIP1/RIP3) and their interaction (proximity ligation) dramatically up-regulated after 5 W in rd10/S1R-/- (versus ..
  76. Chirieleison S, Kertesy S, Abbott D. Synthetic Biology Reveals the Uniqueness of the RIP Kinase Domain. J Immunol. 2016;196:4291-7 pubmed publisher
    ..These findings suggest that RIPK2's kinase domain is functionally unique compared with other RIPK family members and that pharmacologic targeting of RIPK2 can be separated from the other RIPKs. ..
  77. Al Lamki R, Lu W, Manalo P, Wang J, Warren A, Tolkovsky A, et al. Tubular epithelial cells in renal clear cell carcinoma express high RIPK1/3 and show increased susceptibility to TNF receptor 1-induced necroptosis. Cell Death Dis. 2016;7:e2287 pubmed publisher
    ..We conclude that most high-grade RCC cells express increased amounts of RIPK1 and RIPK3 and are poised to undergo necroptosis in response to TNFR1 signaling. ..
  78. Pescatore A, Esposito E, Dráber P, Walczak H, Ursini M. NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II. Cell Death Dis. 2016;7:e2346 pubmed publisher
    ..Alteration of this process may result in differing cellular outcomes and, consequently, also pathological effects in IP patients with different NEMO mutations. ..
  79. Yang C, Li J, Yu L, Zhang Z, Xu F, Jiang L, et al. Regulation of RIP3 by the transcription factor Sp1 and the epigenetic regulator UHRF1 modulates cancer cell necroptosis. Cell Death Dis. 2017;8:e3084 pubmed publisher
    Receptor-interacting kinase-3 (RIP3) is a key regulator of necroptosis. It has been shown that the expression of RIP3 is silenced in most cancer cells and tissues due to genomic methylation...
  80. Cheng Z, Shang Y, Gao S, Zhang T. Overexpression of U1 snRNA induces decrease of U1 spliceosome function associated with Alzheimer's disease. J Neurogenet. 2017;:1-7 pubmed publisher
    ..These findings not only helped researchers better understand the functions of U1 snRNA, but also paved the way to reveal the mechanisms of AD from a different point of view and may find a new therapeutic target for the disease...
  81. Sagulenko V, Vitak N, Vajjhala P, Vince J, Stacey K. Caspase-1 Is an Apical Caspase Leading to Caspase-3 Cleavage in the AIM2 Inflammasome Response, Independent of Caspase-8. J Mol Biol. 2018;430:238-247 pubmed publisher
    ..Initiation of redundant cell death pathways is likely to be a strategy for coping with pathogen interference in death processes. ..
  82. Chang X, Wang L, Wang Z, Wu S, Zhu X, Hu S, et al. TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3. Sci Rep. 2017;7:16111 pubmed publisher
    Receptor-interacting protein kinase 3 (RIP3) is a critical initiator in mediating necroptosis induced by tumor necrosis factor alpha (TNF?) in L929 cells, so knockdown of RIP3 inhibits TNF?-induced L929 cell necroptosis...
  83. Yang T, Cao C, Yang J, Liu T, Lei X, Zhang Z, et al. miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11. Redox Biol. 2018;15:159-169 pubmed publisher
    ..and observed that overexpression of miR-200a-5p spark the receptor interacting serine/threonine kinase 3 (RIP3)-dependent necroptosis in vivo and in vitro...
  84. Feng S, Ma L, Yang Y, Wu M. Truncated RIP3 (tRIP3) acts upstream of FADD to induce apoptosis in the human hepatocellular carcinoma cell line QGY-7703. Biochem Biophys Res Commun. 2006;347:558-65 pubmed
    b>RIP3 (receptor-interacting protein 3) is a serine/threonine kinase that promotes apoptosis in various cell types. The C-terminal domain of RIP3 is critical for its apoptosis induction...
  85. Jeong M, Park J, Jang S. Cloning, overexpression, purification, and characterization of receptor-interacting protein 3 truncation in Escherichia coli. Appl Biochem Biotechnol. 2007;141:175-86 pubmed
    To facilitate structural studies of receptor-interacting protein 3 (RIP3), we developed a large-scale expression system of a glutathione-S-transferase (GST) fused with an 82 amino acid RIP3 protein in Escherichia coli...
  86. Shahsavari Z, Karami Tehrani F, Salami S, Ghasemzadeh M. RIP1K and RIP3K provoked by shikonin induce cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway. Tumour Biol. 2016;37:4479-91 pubmed publisher
    ..The present results shed a new light on the possible treatment of drug-resistant triple negative breast cancer. ..
  87. Yu X, Li Y, Chen Q, Su C, Zhang Z, Yang C, et al. Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1. J Virol. 2016;90:1088-95 pubmed publisher
    Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis...
  88. Petrie E, Hildebrand J, Murphy J. Insane in the membrane: a structural perspective of MLKL function in necroptosis. Immunol Cell Biol. 2017;95:152-159 pubmed publisher
    ..Here, we discuss the insights gleaned from structural and biophysical studies of MLKL and highlight the known unknowns surrounding MLKL's mechanism of action and activation...
  89. Hou X, Yang C, Zhang L, Hu T, Sun D, Cao H, et al. Killing colon cancer cells through PCD pathways by a novel hyaluronic acid-modified shell-core nanoparticle loaded with RIP3 in combination with chloroquine. Biomaterials. 2017;124:195-210 pubmed publisher
    ..In this study, chloroquine (CQ) was found to significantly upregulate receptor-interacting protein kinase 3 (RIP3) expression, and RIP3 were involved in CQ-related autophagy...
  90. Cekay M, Roesler S, Frank T, Knuth A, Eckhardt I, Fulda S. Smac mimetics and type II interferon synergistically induce necroptosis in various cancer cell lines. Cancer Lett. 2017;410:228-237 pubmed publisher
    ..e. receptor-interacting protein (RIP) 1, RIP3 or mixed lineage kinase domain-like pseudokinase (MLKL), significantly protects from BV6/IFNγ-induced cell death...
  91. Dziedzic S, Su Z, Jean Barrett V, Najafov A, Mookhtiar A, Amin P, et al. ABIN-1 regulates RIPK1 activation by linking Met1 ubiquitylation with Lys63 deubiquitylation in TNF-RSC. Nat Cell Biol. 2018;20:58-68 pubmed publisher
    ..We propose that ABIN-1 provides a critical link between Met1 ubiquitylation mediated by the LUBAC complex and Lys63 deubiquitylation by phospho-A20 to modulate the activation of RIPK1. ..
  92. Harris K, Morosky S, Drummond C, Patel M, Kim C, Stolz D, et al. RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells. Cell Host Microbe. 2015;18:221-32 pubmed publisher
    Receptor interacting protein kinase-3 (RIP3) is an essential kinase for necroptotic cell death signaling and has been implicated in antiviral cell death signaling upon DNA virus infection...