TR4

Summary

Gene Symbol: TR4
Description: nuclear receptor subfamily 2 group C member 2
Alias: TAK1, TR4, nuclear receptor subfamily 2 group C member 2, Nuclear hormone receptor TR4, orphan nuclear receptor TAK1, orphan nuclear receptor TR4, orphan receptor TR4, testicular nuclear receptor 4
Species: human
Products:     TR4

Top Publications

  1. Chang C, da Silva S, Ideta R, Lee Y, Yeh S, Burbach J. Human and rat TR4 orphan receptors specify a subclass of the steroid receptor superfamily. Proc Natl Acad Sci U S A. 1994;91:6040-4 pubmed
    ..3 (human) and 65.4 (rat) kDa. The amino acid sequence of this protein, called TR4 orphan receptor, is closely related to the previously identified TR2 orphan receptor...
  2. Suzuki S, Singhirunnusorn P, Mori A, Yamaoka S, Kitajima I, Saiki I, et al. Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-kappaB. J Biol Chem. 2007;282:25177-81 pubmed
    ..Transforming growth factor-beta-activated kinase 1 (TAK1) has been shown to play a critical role in these transcription factors...
  3. Tanabe O, Shen Y, Liu Q, Campbell A, Kuroha T, Yamamoto M, et al. The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription. Genes Dev. 2007;21:2832-44 pubmed
    When the orphan nuclear receptors TR2 and TR4, the DNA-binding subunits of the DRED repressor complex, are forcibly expressed in erythroid cells of transgenic mice, embryos exhibit a transient mid-gestational anemia as a consequence of a ..
  4. O Geen H, Lin Y, Xu X, Echipare L, Komashko V, He D, et al. Genome-wide binding of the orphan nuclear receptor TR4 suggests its general role in fundamental biological processes. BMC Genomics. 2010;11:689 pubmed publisher
    The orphan nuclear receptor TR4 (human testicular receptor 4 or NR2C2) plays a pivotal role in a variety of biological and metabolic processes. With no known ligand and few known target genes, the mode of TR4 function was unclear...
  5. Lee C, Chinpaisal C, Wei L. A novel nuclear receptor heterodimerization pathway mediated by orphan receptors TR2 and TR4. J Biol Chem. 1998;273:25209-15 pubmed
    A unique heterodimerization pathway involving orphan receptors TR2 and TR4 is demonstrated. TR2 and TR4 preferentially form heterodimers in solution as well as on DNA elements containing a direct repeat-5 (DR5)...
  6. Lee Y, Shyr C, Thin T, Lin W, Chang C. Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily. Proc Natl Acad Sci U S A. 1999;96:14724-9 pubmed
    ..Here we demonstrate that the AR can interact with the testicular orphan receptor-4 (TR4) and function as a repressor to down-regulate the TR4 target genes by preventing the TR4 binding to its target DNA...
  7. Shyr C, Hu Y, Kim E, Chang C. Modulation of estrogen receptor-mediated transactivation by orphan receptor TR4 in MCF-7 cells. J Biol Chem. 2002;277:14622-8 pubmed
    The human testicular orphan receptor 4 (TR4) is a member of the nuclear receptor superfamily that shows a broad tissue distribution with higher expression in the nervous system and male reproductive tract...
  8. Tanabe O, Katsuoka F, Campbell A, Song W, Yamamoto M, Tanimoto K, et al. An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer. EMBO J. 2002;21:3434-42 pubmed
    ..DRED is a 540 kDa complex; sequence determination showed that it contains the nuclear orphan receptors TR2 and TR4. TR2 and TR4 form a heterodimer that binds to the epsilon and gamma promoter DR1 sites...
  9. Lee Y, Lee H, Chang C. Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily. J Steroid Biochem Mol Biol. 2002;81:291-308 pubmed
    The human testicular receptor 2 (TR2) and TR4 orphan receptors are two evolutionarily related proteins belonging to the nuclear receptor superfamily...

More Information

Publications123 found, 100 shown here

  1. Takaesu G, Surabhi R, Park K, Ninomiya Tsuji J, Matsumoto K, Gaynor R. TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol. 2003;326:105-15 pubmed
    ..we utilized small interfering RNAs (siRNAs) directed against IKKalpha, IKKbeta and the upstream regulatory kinase TAK1 in order to better define their roles in cytokine-induced activation of the NF-kappaB pathway...
  2. Ishitani T, Takaesu G, Ninomiya Tsuji J, Shibuya H, Gaynor R, Matsumoto K. Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBO J. 2003;22:6277-88 pubmed
    ..b>TAK1, a MAPKKK, is critical for both IL-1- and TNF-induced activation of the NF-kappaB pathway...
  3. Huq M, Gupta P, Tsai N, Wei L. Modulation of testicular receptor 4 activity by mitogen-activated protein kinase-mediated phosphorylation. Mol Cell Proteomics. 2006;5:2072-82 pubmed
    Testicular receptor 4 (TR4) is an orphan member of the nuclear receptor superfamily. Despite the lack of identified ligands, its functional role has been demonstrated both in animals and cell cultures...
  4. Zhou X, Suino Powell K, Xu Y, Chan C, Tanabe O, Kruse S, et al. The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor. J Biol Chem. 2011;286:2877-85 pubmed publisher
    ..Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation...
  5. Dey N, Liu T, Garofalo R, Casola A. TAK1 regulates NF-?B and AP-1 activation in airway epithelial cells following RSV infection. Virology. 2011;418:93-101 pubmed publisher
    ..Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced ..
  6. Shi L, Cui S, Engel J, Tanabe O. Lysine-specific demethylase 1 is a therapeutic target for fetal hemoglobin induction. Nat Med. 2013;19:291-4 pubmed publisher
    ..LSD1 is thus a promising therapeutic target for ?-globin induction, and tranylcypromine may serve as a lead compound for the development of a new ?-globin inducer. ..
  7. Li Z, Sun B, Gong T, Guo S, Zhang J, Wang J, et al. GNAI1 and GNAI3 Reduce Colitis-Associated Tumorigenesis in Mice by Blocking IL6 Signaling and Downregulating Expression of GNAI2. Gastroenterology. 2019;: pubmed publisher
    ..Incubation of MDSCs or MEFs with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2...
  8. Liu Y, Li J, Chen S, Huang H, Cai H. The rLrp of Mycobacterium tuberculosis inhibits proinflammatory cytokine production and downregulates APC function in mouse macrophages via a TLR2-mediated PI3K/Akt pathway activation-dependent mechanism. Cell Mol Immunol. 2016;13:729-746 pubmed publisher
    ..clustering of TNF receptor-associated factor 6 and with interleukin-1 receptor-associated kinase 1 binding to TAK1. Furthermore, rLrp did not attenuate proinflammatory cytokines or the expression of CD86 and major ..
  9. Yuan R, Huang L, Du L, Feng J, Li J, Luo Y, et al. Dihydrotanshinone exhibits an anti-inflammatory effect in vitro and in vivo through blocking TLR4 dimerization. Pharmacol Res. 2019;142:102-114 pubmed publisher
    ..primary response gene 88 (MyD88) and the expression of transforming growth factor-b (TGF-b)-activated kinase 1 (p-TAK1) were disturbed by the inhibition of TLR4 dimerization...
  10. Han X, Zhang F, Tan X, Liu L, Ma W, Ou Yang H, et al. EPO modified MSCs can inhibit asthmatic airway remodeling in an animal model. J Cell Biochem. 2018;119:1008-1016 pubmed publisher
    ..activation state of transforming growth factor-? 1 (TGF-?1), Transforming growth factor beta-activated kinase 1 (TAK1), and p38 Mitogen Activated Protein Kinase (p38MAPK) signaling was detected by Real-Time PCR and Western blotting...
  11. Zhang Y, Guo H, Cheng B, Su T, Fu X, Li T, et al. Dingchuan tang essential oil inhibits the production of inflammatory mediators via suppressing the IRAK/NF-κB, IRAK/AP-1, and TBK1/IRF3 pathways in lipopolysaccharide-stimulated RAW264.7 cells. Drug Des Devel Ther. 2018;12:2731-2748 pubmed publisher
    ..kinase α/β (IKKα/β), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), TGF β-activated kinase 1 (TAK1), TANK-binding kinase 1 (TBK1), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (..
  12. Tian L, Li H, Li Y, Liu K, Sun Y, Cong Z, et al. A Combination of Chitosan, Cellulose, and Seaweed Polysaccharide Inhibits Postoperative Intra-abdominal Adhesion in Rats. J Pharmacol Exp Ther. 2018;364:399-408 pubmed publisher
    ..In addition, the activity of kinases [e.g., transforming growth factor-activated kinase 1 (TAK1), c-Jun N-terminal kinase (JNK)/Stress-activated Protein Kinase (SAPK), and p38] in the mitogen-activated protein ..
  13. Yin J, Li H, Meng C, Chen D, Chen Z, Wang Y, et al. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/?-arrestin2/TGF-? activated kinase-1 binding protein-1 signaling pathway. Int J Biochem Cell Biol. 2016;75:11-22 pubmed publisher
    ..In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor ? activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through ..
  14. Li H, Yoon J, Won H, Ji H, Yuk H, Park K, et al. Isotrifoliol inhibits pro-inflammatory mediators by suppression of TLR/NF-κB and TLR/MAPK signaling in LPS-induced RAW264.7 cells. Int Immunopharmacol. 2017;45:110-119 pubmed publisher
    ..including mRNA expression of TNF receptor associated factor 6, transforming growth factor beta-activated kinase 1 (TAK1), TAK1 binding protein 2 (TAB2), and TAB3...
  15. Kim H, Kim M, Cho J. Alisma canaliculatum ethanol extract suppresses inflammatory responses in LPS-stimulated macrophages, HCl/EtOH-induced gastritis, and DSS-triggered colitis by targeting Src/Syk and TAK1 activities. J Ethnopharmacol. 2018;219:202-212 pubmed publisher
    ..activating these transcription factors, we found that Src and Syk, as well as molecular association between TAK1 and mitogen-activated protein kinase kinase 4/7 (MKK4/7), were targeted by Ac-EE...
  16. Lozhkin A, Vendrov A, Pan H, Wickline S, Madamanchi N, Runge M. NADPH oxidase 4 regulates vascular inflammation in aging and atherosclerosis. J Mol Cell Cardiol. 2017;102:10-21 pubmed publisher
    ..p5RHH peptide-mediated knockdown of TGFβ-activated kinase 1 (TAK1, also known as Map3k7), Jun, and Rela, but not Nfkb2, downregulated TGFβ1-induced Nox4 expression in VSMCs...
  17. Guesmi F, Prasad S, Tyagi A, Landoulsi A. Antinflammatory and anticancer effects of terpenes from oily fractions of Teucruim alopecurus, blocker of I?B? kinase, through downregulation of NF-?B activation, potentiation of apoptosis and suppression of NF-?B-regulated gene expression. Biomed Pharmacother. 2017;95:1876-1885 pubmed publisher
    ..Finally, the activation of nuclear factor-?B induced by different plasmids (TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKK?) was inhibited following treatment with TA-1...
  18. Mondal T, Bag I, Sncvl P, Garikapati K, Bhadra U, Pal Bhadra M. Two way controls of apoptotic regulators consign DmArgonaute-1 a better clasp on it. PLoS ONE. 2018;13:e0190548 pubmed publisher
    ..Ago-1 stimulates phosphorylation of JNK through transforming growth factor-β activated kinase 1- hemipterous (Tak1-hep) axis of JNK pathway...
  19. Li M, Song K, Huang X, Fu S, Zeng Q. GDF‑15 prevents LPS and D‑galactosamine‑induced inflammation and acute liver injury in mice. Int J Mol Med. 2018;42:1756-1764 pubmed publisher
    ..against LPS‑induced nuclear factor (NF)‑κB pathway activation by regulating TGFβ‑activated kinase 1 (TAK1) phosphorylation in Kupffer cells...
  20. Franz S, Rennert P, Woznik M, Grützke J, Lüdde A, Arriero Pais E, et al. Mumps Virus SH Protein Inhibits NF-κB Activation by Interacting with Tumor Necrosis Factor Receptor 1, Interleukin-1 Receptor 1, and Toll-Like Receptor 3 Complexes. J Virol. 2017;91: pubmed publisher
    ..NF-κB activation, and that this inhibition occurs upstream of the NF-κB pathway components TRAF2, TRAF6, and TAK1. Since SH coimmunoprecipitated with tumor necrosis factor receptor 1 (TNFR1), RIP1, and IRAK1, we hypothesize that ..
  21. Wang K, Li S, Gao Y, Feng X, Liu W, Luo R, et al. BCL3 regulates RANKL-induced osteoclastogenesis by interacting with TRAF6 in bone marrow-derived macrophages. Bone. 2018;114:257-267 pubmed publisher
    ..As an adaptor protein of E3 ligase function, TRAF6 regulates NF-κB signaling via TAK1 and I-κB kinase (IKK) activation...
  22. Karwi Q, Zhang L, Wagg C, Wang W, Ghandi M, Thai D, et al. Targeting the glucagon receptor improves cardiac function and enhances insulin sensitivity following a myocardial infarction. Cardiovasc Diabetol. 2019;18:1 pubmed publisher
    ..The MI-induced increase in the phosphorylation of transforming growth factor β-activated kinase 1 (p-TAK1) and p38 MAPK was also reduced by mAb A treatment...
  23. van t Wout E, van Schadewijk A, van Boxtel R, Dalton L, Clarke H, Tommassen J, et al. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells. PLoS Pathog. 2015;11:e1004946 pubmed publisher
    ..Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA...
  24. Gong L, Wang H, Sun X, Liu C, Duan C, Cai R, et al. Toll-Interleukin 1 Receptor domain-containing adaptor protein positively regulates BV2 cell M1 polarization. Eur J Neurosci. 2016;43:1674-82 pubmed publisher
    ..Kinase 1/I-Kappa-B Kinase /Nuclear Factor of Kappa Light Polypeptide Gene Enhancer in B-Cells (TAK1/IKK/NF-?B) signalling pathway and the phosphorylation of Akt and mitogen-activated protein kinases, which were ..
  25. Gupta P, Das P, Ukil A. Antileishmanial effect of 18β-glycyrrhetinic acid is mediated by Toll-like receptor-dependent canonical and noncanonical p38 activation. Antimicrob Agents Chemother. 2015;59:2531-9 pubmed publisher
    ..was attributed to an autophosphorylation event ensured by the transforming growth factor β-activated kinase 1 (TAK1)-binding protein 1 (TAB1)-p38 interaction and was completely abolished upon pretreatment with SB203580 in DN MKK3/6 ..
  26. Gong J, Li Z, Guo S, Zhang X, Zhang P, Zhao G, et al. Neuron-Specific Tumor Necrosis Factor Receptor-Associated Factor 3 Is a Central Regulator of Neuronal Death in Acute Ischemic Stroke. Hypertension. 2015;66:604-16 pubmed publisher
    ..Mechanistically, we showed that TRAF3 interacts with transforming growth factor-β-activated kinase 1 (TAK1) and potentiates phosphorylation and activation of TAK1...
  27. Song H, Shin I, Woo S, Lee S, Sung M, Ryu H, et al. Piscroside C, a novel iridoid glycoside isolated from Pseudolysimachion rotundum var. subinegrum suppresses airway inflammation induced by cigarette smoke. J Ethnopharmacol. 2015;170:20-7 pubmed publisher
    ..by inhibiting NF-κB activation, as resulting decrease in the phosphorylation of IKKβ, IκBα and TAK1 in TNF-α-stimulated H292 cells...
  28. Lin J, Lee D, Choi Y, Lee S. The scaffold protein RACK1 mediates the RANKL-dependent activation of p38 MAPK in osteoclast precursors. Sci Signal. 2015;8:ra54 pubmed publisher
    ..ubiquitin ligase TRAF6 [tumor necrosis factor (TNF) receptor (TNFR)-associated factor 6] and the associated kinase TAK1 [transforming growth factor-β (TGF-β)-activated kinase 1] are key components of the signaling pathways that ..
  29. Senol S, Temiz M, Guden D, Cecen P, Sari A, Sahan Firat S, et al. Contribution of PPARα/β/γ, AP-1, importin-α3, and RXRα to the protective effect of 5,14-HEDGE, a 20-HETE mimetic, against hypotension, tachycardia, and inflammation in a rat model of septic shock. Inflamm Res. 2016;65:367-87 pubmed publisher
    We have previously demonstrated that downregulation of the MyD88/TAK1-dependent signaling pathway associated with increased CYP4A1 expression and 20-HETE formation participates in the protective effect of N-(20-hydroxyeicosa-5[Z],14[Z]-..
  30. Luo X, Chen Y, Lv G, Zhou Z, Chen J, Mo X, et al. Adenovirus-Mediated Small Interfering RNA Targeting TAK1 Ameliorates Joint Inflammation with Collagen-Induced Arthritis in Mice. Inflammation. 2017;40:894-903 pubmed publisher
    Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators...
  31. Young W, Smith S, Chang C. Induction of the intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFRalpha) gene by the TR4 orphan receptor. A member of steroid receptor superfamily. J Biol Chem. 1997;272:3109-16 pubmed
    ..the 5th intron of the alpha component of the ciliary neurotrophic factor receptor (CNTFRalpha) gene for the human TR4 orphan receptor (TR4). Electrophoretic mobility shift assay showed a specific binding with high affinity (Kd = 0...
  32. Zhao Y, Tang Z, Zhu X, Wang X, Wang C, Zhang W, et al. TAB3 involves in hepatic insulin resistance through activation of MAPK pathway. Gen Comp Endocrinol. 2015;224:228-34 pubmed publisher
    ..Considering the relationship between transforming growth factor β-activated kinase (TAK1) and MAPK pathway, we assumed TAB3 involved in insulin resistance through activation of MAPK pathway...
  33. Sbiera S, Deutschbein T, Weigand I, Reincke M, Fassnacht M, Allolio B. The New Molecular Landscape of Cushing's Disease. Trends Endocrinol Metab. 2015;26:573-83 pubmed publisher
    ..understood until the past few years, when several proteins and genes [such as testicular orphan nuclear receptor 4 (TR4) and heat shock protein 90 (HSP90)] were found to play key roles in the disease...
  34. Chen H, Liu Y, Li D, Song J, Xia M. PGC-1β suppresses saturated fatty acid-induced macrophage inflammation by inhibiting TAK1 activation. IUBMB Life. 2016;68:145-55 pubmed publisher
    ..Mechanistically, we revealed that TGF-β-activated kinase 1 (TAK1) and its adaptor protein TAK1 binding protein 1 (TAB1) played a dominant role in the regulatory effects of PGC-1β..
  35. Wang S, Li H, Lu K, Qian Z, Weng S, He J, et al. Identification and characterization of transforming growth factor ?-activated kinase 1 from Litopenaeus vannamei involved in anti-bacterial host defense. Fish Shellfish Immunol. 2016;52:278-88 pubmed publisher
    LvTAK1, a member of transforming growth factor ?-activated kinase 1 (TAK1) families, has been identified from Litopenaeus vannamei in this study...
  36. Zhao Y, Zhang W, Liu X, Zhang P, Hao Y, Li L, et al. Hydrogen Sulfide and/or Ammonia Reduces Spermatozoa Motility through AMPK/AKT Related Pathways. Sci Rep. 2016;6:37884 pubmed publisher
    ..in Na+/K+ ATPase activity), transforming growth factor (TGF?) activated kinase-1 (TAK1) activation, and AKT deactivation stimulated AMPK, which caused a decline in boar spermatozoa motility...
  37. Yeh D, Wu C, Chin Y, Lu C, Wang Y, Chen M. Mechanisms of human lymphotoxin beta receptor activation on upregulation of CCL5/RANTES production. Int Immunopharmacol. 2015;28:220-9 pubmed publisher
    ..In addition, dominant negative mutants of ASK1, TAK1, and MEKK1 inhibited LTβR-induced RANTES expression...
  38. Sumiya E, Negishi Koga T, Nagai Y, Suematsu A, Suda T, Shinohara M, et al. Phosphoproteomic analysis of kinase-deficient mice reveals multiple TAK1 targets in osteoclast differentiation. Biochem Biophys Res Commun. 2015;463:1284-90 pubmed publisher
    b>TAK1 (encoded by Map3k7) is a mitogen-activated protein kinase kinase kinase (MAP3K), which activates the transcription factors AP-1 and NF-κB in response to receptor activator of NF-κB ligand (RANKL) stimulation, thus constituting ..
  39. Hirata Y, Takahashi M, Morishita T, Noguchi T, Matsuzawa A. Post-Translational Modifications of the TAK1-TAB Complex. Int J Mol Sci. 2017;18: pubmed publisher
    Transforming growth factor-? (TGF-?)-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that is activated by growth factors and cytokines such as TGF-?, IL-1?, and TNF-?, and ..
  40. Ji K, Zhang P, Zhang J, Fan R, Liu Y, Yang S, et al. MicroRNA 143-5p regulates alpaca melanocyte migration, proliferation, and melanogenesis. Exp Dermatol. 2017;: pubmed publisher
    ..Prediction analysis revealed that miR-143-5p could regulate TGF-?-activated kinase 1 (TAK1) expression, which we confirmed by luciferase reporter assay, indicating that miR-143-5p controls TAK1 expression ..
  41. Aonuma T, Takehara N, Maruyama K, Kabara M, Matsuki M, Yamauchi A, et al. Apoptosis-Resistant Cardiac Progenitor Cells Modified With Apurinic/Apyrimidinic Endonuclease/Redox Factor 1 Gene Overexpression Regulate Cardiac Repair After Myocardial Infarction. Stem Cells Transl Med. 2016;5:1067-78 pubmed publisher
    ..APE1 overexpression inhibited CPC apoptosis with activation of transforming growth factor ?-activated kinase 1 (TAK1) and nuclear factor (NF)-?B...
  42. Zhang Y, Mühlen S, Oates C, Pearson J, Hartland E. Identification of a Distinct Substrate-binding Domain in the Bacterial Cysteine Methyltransferase Effectors NleE and OspZ. J Biol Chem. 2016;291:20149-62 pubmed publisher
    ..NleE inactivates the ubiquitin chain binding activity of host proteins TAK1-binding proteins 2 and 3 (TAB2 and TAB3) by modifying the Npl4 zinc finger domain through S-adenosyl methionine-..
  43. Lim R, Barker G, Lappas M. TRADD, TRAF2, RIP1 and TAK1 are required for TNF-α-induced pro-labour mediators in human primary myometrial cells. Am J Reprod Immunol. 2017;78: pubmed publisher
    ..factor 2 (TRAF2), receptor interacting protein 1 (RIP1) and transforming growth factor beta-activated kinase 1 (TAK1) in TNF-α-induced formation of pro-labour mediators...
  44. Wang W, Jia W, Hu B, Pan Y. RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma. Oncotarget. 2017;8:26434-26447 pubmed publisher
    ..VEGFR2/KDR, Akt/PKB/Rac, S6 Ribosomal Protein and c-Abl, while the phosphorylation of HSP27, p38 MAPK, Chk2 and TAK1 increased significantly...
  45. Park S, Kwak J, Jung S, Ahn B, Cho W, Yun C, et al. Piperidylmethyloxychalcone improves immune-mediated acute liver failure via inhibiting TAK1 activity. Exp Mol Med. 2017;49:e392 pubmed publisher
    ..As a mechanism, PMOC inhibited the catalytic activity of TGF-?-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and ..
  46. Malireddi R, Gurung P, Mavuluri J, Dasari T, Klco J, Chi H, et al. TAK1 restricts spontaneous NLRP3 activation and cell death to control myeloid proliferation. J Exp Med. 2018;215:1023-1034 pubmed publisher
    ..Here, we show that TGF-? activated kinase-1 (TAK1) is a central regulator of NLRP3 inflammasome activation and spontaneous cell death...
  47. Murphy M, Xiong Y, Pattabiraman G, Qiu F, Medvedev A. Pellino-1 Positively Regulates Toll-like Receptor (TLR) 2 and TLR4 Signaling and Is Suppressed upon Induction of Endotoxin Tolerance. J Biol Chem. 2015;290:19218-32 pubmed publisher
    ..Mechanistically, Pellino-1 increased LPS-driven K63-linked polyubiquitination of IRAK1, TBK1, TAK1, and phosphorylation of TBK1 and IFN regulatory factor 3...
  48. Cong Q, Jia H, Biswas S, Li P, Qiu S, Deng Q, et al. p38α MAPK Regulates Lineage Commitment and OPG Synthesis of Bone Marrow Stromal Cells to Prevent Bone Loss under Physiological and Pathological Conditions. Stem Cell Reports. 2016;6:566-578 pubmed publisher
    ..p38α regulates BM-MSC osteogenic commitment through TAK1-NF-κB signaling and osteoclastogenesis through osteoprotegerin (OPG) production by BM-MSCs...
  49. Tan L, Gurbani D, Weisberg E, Hunter J, Li L, Jones D, et al. Structure-guided development of covalent TAK1 inhibitors. Bioorg Med Chem. 2017;25:838-846 pubmed publisher
    b>TAK1 (transforming growth factor-?-activated kinase 1) is an essential intracellular mediator of cytokine and growth factor signaling and a potential therapeutic target for the treatment of immune diseases and cancer...
  50. Yang Y, Qiu Y, Tang M, Wu Z, Hu W, Chen C. Expression and function of transforming growth factor‑β‑activated protein kinase 1 in gastric cancer. Mol Med Rep. 2017;16:3103-3110 pubmed publisher
    ..the expression and role of transforming growth factor (TGF) ‑β‑activated protein kinase 1 (TAK1) in human gastric cancer...
  51. Liu S, Yan S, Lee Y, Liu N, Ting H, Li G, et al. Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via Cockayne syndrome B protein-mediated transcription-coupled DNA repair. J Biol Chem. 2011;286:38103-8 pubmed publisher
    ..We report here that testicular nuclear receptor 4 (TR4), a member of the nuclear receptor family, modulates DNA repair specifically through the ..
  52. Le Goff C, Rogers C, Le Goff W, Pinto G, Bonnet D, Chrabieh M, et al. Heterozygous Mutations in MAP3K7, Encoding TGF-?-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome. Am J Hum Genet. 2016;99:407-13 pubmed publisher
    ..MAP3K7 encodes transforming growth factor ? (TGF-?)-activated kinase 1 (TAK1), which is involved in the mitogen-activated protein kinase (MAPK)-p38 signaling pathway...
  53. Strickson S, Emmerich C, Goh E, Zhang J, Kelsall I, MacArtney T, et al. Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling. Proc Natl Acad Sci U S A. 2017;114:E3481-E3489 pubmed publisher
    ..in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation ..
  54. Al Nabhani Z, Montcuquet N, Roy M, Dussaillant M, Hugot J, Barreau F. Complementary Roles of Nod2 in Hematopoietic and Nonhematopoietic Cells in Preventing Gut Barrier Dysfunction Dependent on MLCK Activity. Inflamm Bowel Dis. 2017;23:1109-1119 pubmed publisher
    ..This MLCK regulation is mediated by TAK1 and RICK-dependent mechanisms...
  55. Mi X, Liu Q, Zhu L, Sang M, Guo L, Shan B. Mechanism of the high coagulation state of breast cancer tissue factor. Eur Rev Med Pharmacol Sci. 2017;21:2167-2171 pubmed
    ..time (APTT), fibrinogen (FIB) and D-dimer body (D-D) level and NF-?B signaling pathway index including P50, p65, TAK1 and I?B? levels...
  56. Xia P, Wang S, Xiong Z, Zhu X, Ye B, Du Y, et al. The ER membrane adaptor ERAdP senses the bacterial second messenger c-di-AMP and initiates anti-bacterial immunity. Nat Immunol. 2018;19:141-150 pubmed publisher
    ..of ERAdP, which in turn led to dimerization of ERAdP, resulting in association with and activation of the kinase TAK1. TAK1 activation consequently initiated activation of the transcription factor NF-κB to induce the production of ..
  57. Zhang F, Yu J, Yang T, Xu D, Chi Z, Xia Y, et al. A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development. J Biol Chem. 2016;291:11466-75 pubmed publisher
    ..We show here that knock-out or knockdown of Tak1 (TGF?-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical ..
  58. Yao P, Hongqian C, Qinghe M, Lanqin S, Jianjun J, Xiaohua Y, et al. Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay. Toxicol Appl Pharmacol. 2016;307:72-80 pubmed publisher
    ..Transforming growth factor-? activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis...
  59. Levin R, Hertz N, Burlingame A, Shokat K, Mukherjee S. Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen. Proc Natl Acad Sci U S A. 2016;113:E4776-83 pubmed publisher
    TGF-? activated kinase 1 (TAK1) is a critical signaling hub responsible for translating antigen binding signals to immune receptors for the activation of the AP-1 and NF-?B master transcriptional programs...
  60. Liu R, Wang G, Liu C, Qiu J, Yan L, Li X, et al. Gene expression profile analysis of dbpA knockdown in colorectal cancer cells. Cell Biol Int. 2016;40:1280-1293 pubmed publisher
    ..Furthermore, Western blot verified that dbpA knockdown directly inhibited the activations of TAK1, p38, and JNK in CRC cells...
  61. Vink P, Smout W, Driessen Engels L, de Bruin A, Delsing D, Krajnc Franken M, et al. In vivo knockdown of TAK1 accelerates bone marrow proliferation/differentiation and induces systemic inflammation. PLoS ONE. 2013;8:e57348 pubmed publisher
    b>TAK1 (TGF-β Activated Kinase 1) is a MAPK kinase kinase, which activates the p38- and JNK-MAPK and NF-κB pathways downstream of receptors such as Toll-Like-, cytokine- and T-cell and B-cell receptors...
  62. Li L, Chen Y, Li J, Yin H, Guo X, Doan J, et al. TAK1 Regulates Myocardial Response to Pathological Stress via NFAT, NFκB, and Bnip3 Pathways. Sci Rep. 2015;5:16626 pubmed publisher
    b>TAK1 (TGFβ-activated kinase-1) signaling is essential in regulating a number of important biological functions, including innate immunity, inflammatory response, cell growth and differentiation, and myocardial homeostasis...
  63. Jiang L, Xu F, He W, Chen L, Zhong H, Wu Y, et al. CD200Fc reduces TLR4-mediated inflammatory responses in LPS-induced rat primary microglial cells via inhibition of the NF-κB pathway. Inflamm Res. 2016;65:521-32 pubmed publisher
    ..TNF-α, iNOS, MCP-1, and COX-2) was monitored by ELISA or real-time PCR, while NF-κB-related signals (MyD88, p-TAK1, TRIF, p-TBK1, p-IRF3, p-IκB, and NF-κB-P65) were assessed by real-time PCR, western blot and/or ..
  64. Li X, Jin Q, Wu Y, Sun P, Jiang S, Zhang Y, et al. Tetrandrine regulates hepatic stellate cell activation via TAK1 and NF-?B signaling. Int Immunopharmacol. 2016;36:263-270 pubmed publisher
    ..TNF-? treatment induced TGF-?-activated kinase-1 (TAK1) and c-Jun N-terminal kinase (JNK) phosphorylation, which were attenuated by tetrandrine...
  65. Ruscher R, Kummer R, Lee Y, Jameson S, Hogquist K. CD8?? intraepithelial lymphocytes arise from two main thymic precursors. Nat Immunol. 2017;18:771-779 pubmed publisher
    ..precursor populations among TCR?+CD4-CD8- thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria...
  66. van den Akker G, van Beuningen H, Vitters E, Koenders M, van de Loo F, van Lent P, et al. Interleukin 1 β-induced SMAD2/3 linker modifications are TAK1 dependent and delay TGFβ signaling in primary human mesenchymal stem cells. Cell Signal. 2017;40:190-199 pubmed publisher
    ..We identified TAK1 kinase activity as crucial for IL1β-induced SMAD2 linker modifications and CAGA12-luciferase activity...
  67. Zhu X, Hu T, Ho M, Wang Y, Yu M, Patel N, et al. Hydroxyurea differentially modulates activator and repressors of ?-globin gene in erythroblasts of responsive and non-responsive patients with sickle cell disease in correlation with Index of Hydroxyurea Responsiveness. Haematologica. 2017;102:1995-2004 pubmed publisher
    ..we examined HU-induced changes in the RNA and protein levels of transcription factors NF-Y, GATA-1, -2, BCL11A, TR4, MYB and NF-E4 that assemble the ?-globin promoter complex and regulate transcription of ?-globin gene...
  68. Liang S, Li Y, Li X, Wang J, Tan F, Han Q, et al. [Mechanism of colon cancer cell apoptosis induced by telocinobufagin: role of oxidative stress and apoptosis pathway]. Nan Fang Yi Ke Da Xue Xue Bao. 2016;36:921-6 pubmed
    ..Telocinobufagin induced phosphorylation of Bad and PARP cleavage, and suppressed phosphorylation of IKB? and TAK1 and expression of survivin in the cells...
  69. Chen Q, Wu S, Wu Y, Chen L, Pang Q. MiR-149 suppresses the inflammatory response of chondrocytes in osteoarthritis by down-regulating the activation of TAK1/NF-?B. Biomed Pharmacother. 2018;101:763-768 pubmed publisher
    ..Real-time PCR was used to detect miR-149 and the mRNA expression of TAK1, western blot was used to detect the protein expression of TAK1...
  70. Zuo L, Zhang F, Zhang H, Zhang X, Wang F, Li C, et al. Genome-wide search for replicable risk gene regions in alcohol and nicotine co-dependence. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:437-44 pubmed publisher
    ..We concluded that the SH3BP5-NR2C2 region on Chromosome 3 might harbor causal loci for alcohol and nicotine co-dependence. ..
  71. Ding X, Yu S, Chen B, Lin S, Chang C, Li G. Recent advances in the study of testicular nuclear receptor 4. J Zhejiang Univ Sci B. 2013;14:171-7 pubmed publisher
    b>Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family...
  72. Lin S, Lin C, Yang D, Izumi K, Yan E, Niu X, et al. The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status. Neoplasia. 2015;17:339-47 pubmed publisher
    ..Here, we found that the potential impact of TZDs on the prostate cancer (PCa) progression might be linked to the TR4 nuclear receptor expression...
  73. Shi L, Xin Q, Chai R, Liu L, Ma Z. Ectopic expressed miR-203 contributes to chronic obstructive pulmonary disease via targeting TAK1 and PIK3CA. Int J Clin Exp Pathol. 2015;8:10662-70 pubmed
    ..Predicted by bioinformatics tools and confirmed by luciferase assay and western blot, we demonstrated that TAK1 and PIK3CA are two direct targets of miR-203...
  74. Du L, Liu Y, Du Y, Wang H, Zhang M, Du Y, et al. Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-15 through PKC?1-TAK1-NF-?B signaling pathway. Virology. 2016;496:166-174 pubmed publisher
    ..In addition, we demonstrated that PRRSV activated NF-?B through PKC?1-induced TAK1 activation. Finally, we demonstrated that PRRSV activated PKC?1 dependent on the participation of TRIF and MAVS...
  75. Jiang L, Pan C, Wang C, Liu B, Han Y, Hu L, et al. Selective suppression of the JNK-MMP2/9 signal pathway by tetramethylpyrazine attenuates neuropathic pain in rats. J Neuroinflammation. 2017;14:174 pubmed publisher
    ..Our study also revealed that the effect of TMP may be dependent on the inhibition of TAK1. Inhibition of astrocyte activation in the spinal cord by tetramethylpyrazine may have utility in the treatment of ..
  76. Lee M, Tanabe O, Shi L, Jearawiriyapaisarn N, Lucas D, Engel J. The orphan nuclear receptor TR4 regulates erythroid cell proliferation and maturation. Blood. 2017;130:2537-2547 pubmed publisher
    The orphan nuclear receptors TR4 (NR2C2) and TR2 (NR2C1) are the DNA-binding subunits of the macromolecular complex, direct repeat erythroid-definitive, which has been shown to repress ?- and ?-globin transcription during ..
  77. Kobayashi A, Kobayashi S, Miyai K, Osawa Y, Horiuchi T, Kato S, et al. TAK1 inhibition ameliorates survival from graft-versus-host disease in an allogeneic murine marrow transplantation model. Int J Hematol. 2018;107:222-229 pubmed publisher
    ..of peripheral monocytes from patients' post-allo-HCT, we detected an upregulation of TGF-?-activated kinase 1 (TAK1), a key regulator of the toll-like receptor signaling pathway...
  78. Zhou H, Qin Y, Ji S, Ling J, Fu J, Zhuang Z, et al. SOX9 activity is induced by oncogenic Kras to affect MDC1 and MCMs expression in pancreatic cancer. Oncogene. 2018;37:912-923 pubmed publisher
    ..Moreover, oncogenic Kras promoted nuclear translocation and transcriptional activity of SOX9 in these cells. TAK1/IκBα/NF-κB pathway contributed to induction of SOX9 by oncogenic Kras, and SOX9 in turn enhanced NF-κB ..
  79. Moschonas A, Kouraki M, Knox P, Thymiakou E, Kardassis D, Eliopoulos A. CD40 induces antigen transporter and immunoproteasome gene expression in carcinomas via the coordinated action of NF-kappaB and of NF-kappaB-mediated de novo synthesis of IRF-1. Mol Cell Biol. 2008;28:6208-22 pubmed publisher
    ..controlled largely by the recruitment of p65 (RelA) NF-kappaB to the IRF-1 promoter following the engagement of a TAK1/IkappaB kinase beta/IkappaBalpha signaling pathway downstream of CD40...
  80. Srivastava R, Burbach B, Shimizu Y. NF-kappaB activation in T cells requires discrete control of IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation and IKKgamma ubiquitination by the ADAP adapter protein. J Biol Chem. 2010;285:11100-5 pubmed publisher
    ..In this study, we identify a novel site in ADAP that is critical for association with the TAK1 kinase. ADAP is critical for recruitment of TAK1 and the CBM complex, but not IKK, to protein kinase C-theta...
  81. Chang Y, Lee T, Chiang A. Quercetin enhances ABCA1 expression and cholesterol efflux through a p38-dependent pathway in macrophages. J Lipid Res. 2012;53:1840-50 pubmed publisher
    ..of p38 by up to 234-fold at 6 h via an activation of the transforming growth factor ?-activated kinase 1 (TAK1) and mitogen-activated kinase kinase 3/6 (MKK3/6)...
  82. Cui W, Xiao N, Xiao H, Zhou H, Yu M, Gu J, et al. ?-TrCP-mediated IRAK1 degradation releases TAK1-TRAF6 from the membrane to the cytosol for TAK1-dependent NF-?B activation. Mol Cell Biol. 2012;32:3990-4000 pubmed publisher
    ..Importantly, ?-TrCP deficiency abolished the translocation TAK1-TRAF6 complex from the membrane to the cytosol, resulting in a diminishment of the IL-1-induced TAK1-dependent ..
  83. Kumawat K, Menzen M, Slegtenhorst R, Halayko A, Schmidt M, Gosens R. TGF-?-activated kinase 1 (TAK1) signaling regulates TGF-?-induced WNT-5A expression in airway smooth muscle cells via Sp1 and ?-catenin. PLoS ONE. 2014;9:e94801 pubmed publisher
    ..We show that TGF-?-activated kinase 1 (TAK1) is a critical mediator of WNT-5A expression as its pharmacological inhibition or siRNA-mediated silencing reduced ..
  84. Cai P, Shi L, Liu V, Tang H, Liu I, Leung T, et al. Elevated TAK1 augments tumor growth and metastatic capacities of ovarian cancer cells through activation of NF-κB signaling. Oncotarget. 2014;5:7549-62 pubmed
    Transforming growth factor (TGF)-β-activating kinase 1 (TAK1) is a serine/threonine kinase which is frequently associated with human cancer progression. However, its functional role in tumorigenesis is still controversial...
  85. Xi F, Liu Y, Wang X, Kong W, Zhao F. LYATK1 potently inhibits LPS-mediated pro-inflammatory response. Biochem Biophys Res Commun. 2016;470:1-8 pubmed publisher
    ..TGF-?-activated kinase1 (TAK1) activation is involved in the process...
  86. Mia S, Castor T, Musculus K, Voelkl J, Alesutan I, Lang F. Role of AMP-activated protein kinase ?1 in angiotensin-II-induced renal Tgfß-activated kinase 1 activation. Biochem Biophys Res Commun. 2016;476:267-272 pubmed publisher
    ..Angiotensin-II increased the phosphorylation of Tak1 (Ser(412)) in renal tissue of Ampk?1(+/+) mice, an effect virtually absent in the Ampk?1(-/-) mice...
  87. Huang F, Peng J, Cheng W, Zhuang Y, Wang L, Li C, et al. MiR-143 Targeting TAK1 Attenuates Pancreatic Ductal Adenocarcinoma Progression via MAPK and NF-?B Pathway In Vitro. Dig Dis Sci. 2017;62:944-957 pubmed publisher
    Transforming growth factor (TGF)-?-activated kinase 1 (TAK1) is one of the major regulators of inflammation-induced cancer cell growth and progression...
  88. Qi Y, Pradipta A, Li M, Zhao X, Lu L, Fu X, et al. Cinchonine induces apoptosis of HeLa and A549 cells through targeting TRAF6. J Exp Clin Cancer Res. 2017;36:35 pubmed publisher
    Cancer cells are known to over-express TRAF6 that is critical for both AKT and TAK1 activations...
  89. Xia Z, Xu G, Yang X, Peng N, Zuo Q, Zhu S, et al. Inducible TAP1 Negatively Regulates the Antiviral Innate Immune Response by Targeting the TAK1 Complex. J Immunol. 2017;198:3690-3704 pubmed publisher
    ..virus infection, TAP1 interacted with the TGF-?-activated kinase (TAK)1 complex and impaired the phosphorylation of TAK1, subsequently suppressing the phosphorylation of the I?B kinase complex and NF-?B inhibitor ? (I?B?) as well as NF-?..
  90. Lu X, Huang C, Zhang Y, Lin Y, Wang X, Li Q, et al. The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1. Sci Rep. 2017;7:8396 pubmed publisher
    ..Co-immunoprecipitations indicated that Us2 interacted with TGF-β activated kinase 1 (TAK1), a serine/threonine kinase essential for NF-κB activation, and Us2 has the ability to regulate the TAK1-mediated ..
  91. Towsley G, Neradilek M, Snow A, Ersek M. Evaluating the Cornell Scale for Depression in Dementia as a proxy measure in nursing home residents with and without dementia. Aging Ment Health. 2012;16:892-901 pubmed publisher
    ..These findings underscore the importance of obtaining resident input when assessing depression in NH residents with dementia, and educating NH nurses in the most effective ways to assess depression. ..
  92. Yang D, Ding X, Luo J, Shan Y, Wang R, Lin S, et al. Increased chemosensitivity via targeting testicular nuclear receptor 4 (TR4)-Oct4-interleukin 1 receptor antagonist (IL1Ra) axis in prostate cancer CD133+ stem/progenitor cells to battle prostate cancer. J Biol Chem. 2013;288:16476-83 pubmed publisher
    ..We found the expression of testicular nuclear receptor 4 (TR4) is significantly higher in PCa CD133(+) stem/progenitor cells compared with CD133(-) non-stem/..