i kappa b kinase

Summary

Summary: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.

Top Publications

  1. Wilson W, Baldwin A. Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase-3alpha/beta in pancreatic cancer. Cancer Res. 2008;68:8156-63 pubmed publisher
    ..These data provide new insight into GSK-3-dependent NF-kappaB regulation and further establish GSK-3 and IKK as potential therapeutic targets for pancreatic cancer. ..
  2. Mbalaviele G, Sommers C, Bonar S, Mathialagan S, Schindler J, Guzova J, et al. A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a tool to correlate IKK-2 activity to the fate and functions of the components of the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models. J Pharmacol Exp Ther. 2009;329:14-25 pubmed publisher
    ..Thus, PHA-408 represents a powerful tool to further gain insight into the mechanisms by which IKK-2 regulates NF-kappaB signaling and validates IKK-2 as a therapeutic target. ..
  3. Renner F, Moreno R, Schmitz M. SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death. Mol Cell. 2010;37:503-15 pubmed publisher
    ..SUMO modification of IKKepsilon is required to trigger phosphorylation of nuclear substrates including NF-kappaB p65, thereby contributing to the antiapoptotic function of NF-kappaB in response to DNA damage. ..
  4. Lei Y, Zhang Y, Cao Y, Edvinsson L, Xu C. Up-regulation of bradykinin receptors in rat bronchi via I kappa B kinase-mediated inflammatory signaling pathway. Eur J Pharmacol. 2010;634:149-61 pubmed publisher
    ..Thus, IKK inhibition might be a promising approach for treatment of airway inflammation and airway hyperresponsiveness that are often seen in asthmatic patients. ..
  5. Zeng W, Xu M, Liu S, Sun L, Chen Z. Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell. 2009;36:315-25 pubmed publisher
    ..Furthermore, we show that replacement of endogenous ubiquitin with its K63R mutant abolishes viral activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in IRF3 activation. ..
  6. Xu M, Skaug B, Zeng W, Chen Z. A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta. Mol Cell. 2009;36:302-14 pubmed publisher
    ..The ubiquitin replacement methodology described here provides a means to investigate the function of polyubiquitin topology in various cellular processes. ..
  7. Chiang S, Bazuine M, Lumeng C, Geletka L, Mowers J, White N, et al. The protein kinase IKKepsilon regulates energy balance in obese mice. Cell. 2009;138:961-75 pubmed publisher
    ..Thus, IKKepsilon may represent an attractive therapeutic target for obesity, insulin resistance, diabetes, and other complications associated with these disorders. ..
  8. Ghosh S, Hayden M. New regulators of NF-kappaB in inflammation. Nat Rev Immunol. 2008;8:837-48 pubmed publisher
    ..As a result, several new NF-kappaB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-kappaB. ..
  9. Solt L, Madge L, May M. NEMO-binding domains of both IKKalpha and IKKbeta regulate IkappaB kinase complex assembly and classical NF-kappaB activation. J Biol Chem. 2009;284:27596-608 pubmed publisher
    ..These findings therefore demonstrate that formation of the heterotrimeric IKKalpha-IKKbeta-NEMO holocomplex absolutely requires two intact NEMO-binding domains. ..
  10. Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell. 2009;136:1098-109 pubmed publisher

Detail Information

Publications62

  1. Wilson W, Baldwin A. Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase-3alpha/beta in pancreatic cancer. Cancer Res. 2008;68:8156-63 pubmed publisher
    ..These data provide new insight into GSK-3-dependent NF-kappaB regulation and further establish GSK-3 and IKK as potential therapeutic targets for pancreatic cancer. ..
  2. Mbalaviele G, Sommers C, Bonar S, Mathialagan S, Schindler J, Guzova J, et al. A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a tool to correlate IKK-2 activity to the fate and functions of the components of the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models. J Pharmacol Exp Ther. 2009;329:14-25 pubmed publisher
    ..Thus, PHA-408 represents a powerful tool to further gain insight into the mechanisms by which IKK-2 regulates NF-kappaB signaling and validates IKK-2 as a therapeutic target. ..
  3. Renner F, Moreno R, Schmitz M. SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death. Mol Cell. 2010;37:503-15 pubmed publisher
    ..SUMO modification of IKKepsilon is required to trigger phosphorylation of nuclear substrates including NF-kappaB p65, thereby contributing to the antiapoptotic function of NF-kappaB in response to DNA damage. ..
  4. Lei Y, Zhang Y, Cao Y, Edvinsson L, Xu C. Up-regulation of bradykinin receptors in rat bronchi via I kappa B kinase-mediated inflammatory signaling pathway. Eur J Pharmacol. 2010;634:149-61 pubmed publisher
    ..Thus, IKK inhibition might be a promising approach for treatment of airway inflammation and airway hyperresponsiveness that are often seen in asthmatic patients. ..
  5. Zeng W, Xu M, Liu S, Sun L, Chen Z. Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell. 2009;36:315-25 pubmed publisher
    ..Furthermore, we show that replacement of endogenous ubiquitin with its K63R mutant abolishes viral activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in IRF3 activation. ..
  6. Xu M, Skaug B, Zeng W, Chen Z. A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta. Mol Cell. 2009;36:302-14 pubmed publisher
    ..The ubiquitin replacement methodology described here provides a means to investigate the function of polyubiquitin topology in various cellular processes. ..
  7. Chiang S, Bazuine M, Lumeng C, Geletka L, Mowers J, White N, et al. The protein kinase IKKepsilon regulates energy balance in obese mice. Cell. 2009;138:961-75 pubmed publisher
    ..Thus, IKKepsilon may represent an attractive therapeutic target for obesity, insulin resistance, diabetes, and other complications associated with these disorders. ..
  8. Ghosh S, Hayden M. New regulators of NF-kappaB in inflammation. Nat Rev Immunol. 2008;8:837-48 pubmed publisher
    ..As a result, several new NF-kappaB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-kappaB. ..
  9. Solt L, Madge L, May M. NEMO-binding domains of both IKKalpha and IKKbeta regulate IkappaB kinase complex assembly and classical NF-kappaB activation. J Biol Chem. 2009;284:27596-608 pubmed publisher
    ..These findings therefore demonstrate that formation of the heterotrimeric IKKalpha-IKKbeta-NEMO holocomplex absolutely requires two intact NEMO-binding domains. ..
  10. Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell. 2009;136:1098-109 pubmed publisher
  11. Clark K, Plater L, Peggie M, Cohen P. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem. 2009;284:14136-46 pubmed publisher
  12. Chariot A. The NF-kappaB-independent functions of IKK subunits in immunity and cancer. Trends Cell Biol. 2009;19:404-13 pubmed publisher
    ..Thus, these recent findings considerably widen the biological roles of these kinases and suggest that a full understanding of the biological roles of IKK alpha and IKK beta requires an exhaustive characterization of their substrates. ..
  13. Mao X, Gluck N, Li D, Maine G, Li H, Zaidi I, et al. GCN5 is a required cofactor for a ubiquitin ligase that targets NF-kappaB/RelA. Genes Dev. 2009;23:849-61 pubmed publisher
    ..Collectively, the data indicate that GCN5 participates in the ubiquitination process as an accessory factor for a ubiquitin ligase, where it provides a novel link between phosphorylation and ubiquitination. ..
  14. Khoshnan A, Ko J, Tescu S, Brundin P, Patterson P. IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin. PLoS ONE. 2009;4:e5768 pubmed publisher
    ..Moreover, IKKbeta-dependent reduction of Bcl-xL is important in this process. Thus, inhibition of IKKbeta may promote neuronal survival in HD as well as other DNA damage-induced neurodegenerative disorders. ..
  15. Sommers C, Thompson J, Guzova J, Bonar S, Rader R, Mathialagan S, et al. Novel tight-binding inhibitory factor-kappaB kinase (IKK-2) inhibitors demonstrate target-specific anti-inflammatory activities in cellular assays and following oral and local delivery in an in vivo model of airway inflammation. J Pharmacol Exp Ther. 2009;330:377-88 pubmed publisher
    ..Together, these results support the potential therapeutic utility of IKK-2 inhibition in inflammatory pulmonary diseases and demonstrate anti-inflammatory efficacy of an inhaled IKK-2 inhibitor in a rat airway model of neutrophilia. ..
  16. Hayden M, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344-62 pubmed publisher
    ..Here, we attempt to synthesize some of the basic principles that have emerged from studies of NF-kappaB, and we aim to generate a more unified view of NF-kappaB regulation. ..
  17. Greten F, Arkan M, Bollrath J, Hsu L, Goode J, Miething C, et al. NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell. 2007;130:918-31 pubmed
    ..These results unravel an unanticipated role for IKKbeta-dependent NF-kappaB signaling in the negative control of IL-1beta production and highlight potential complications of long-term IKKbeta inhibition. ..
  18. Solt L, May M. The IkappaB kinase complex: master regulator of NF-kappaB signaling. Immunol Res. 2008;42:3-18 pubmed publisher
  19. Bednarski B, Ding X, Coombe K, Baldwin A, Kim H. Active roles for inhibitory kappaB kinases alpha and beta in nuclear factor-kappaB-mediated chemoresistance to doxorubicin. Mol Cancer Ther. 2008;7:1827-35 pubmed publisher
    ..Moreover, we show that IKKalpha plays a critical role in NF-kappaB-mediated chemoresistance in response to doxorubicin and may serve as a potential target in combinational strategies to improve chemotherapeutic response. ..
  20. Devaraj S, Jialal I. Increased secretion of IP-10 from monocytes under hyperglycemia is via the TLR2 and TLR4 pathway. Cytokine. 2009;47:6-10 pubmed publisher
    ..Thus, we demonstrate increased circulating and monocytic IP-10 in T1DM. Down-regulation of TLR2 and TLR4 abrogates HG-induced IP-10 release via NF-kappaB inhibition. ..
  21. Jin R, Lho Y, Connelly L, Wang Y, Yu X, Saint Jean L, et al. The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth. Cancer Res. 2008;68:6762-9 pubmed publisher
    ..Thus, the NF-kappaB pathway may be a potential target for therapy against androgen-independent prostate cancer. ..
  22. Doti N, Marasco D, Pedone C, Sabatella M, Ruvo M. Optimizing a kinase assay for IKKbeta on an HTS station. J Biomol Screen. 2009;14:1263-8 pubmed publisher
    ..Under the optimized conditions, the assay Z' factor calculated over 192 data points has an optimized value of 0.881 and allows the testing of 94 molecules in quadruplicate in 140 min. ..
  23. Nagai K, Takahashi Y, Mikami I, Fukusima T, Oike H, Kobori M. The hydroxyflavone, fisetin, suppresses mast cell activation induced by interaction with activated T cell membranes. Br J Pharmacol. 2009;158:907-19 pubmed publisher
    ..Fisetin may protect against the progression of inflammatory diseases by limiting interactions between mast cells and activated T cells. ..
  24. Thomas G, Zhang L, Blackwell K, Habelhah H. Phosphorylation of TRAF2 within its RING domain inhibits stress-induced cell death by promoting IKK and suppressing JNK activation. Cancer Res. 2009;69:3665-72 pubmed publisher
  25. Nagarajan S, Choo H, Cho Y, Oh K, Lee B, Shin K, et al. IKKbeta inhibitors identification part II: ligand and structure-based virtual screening. Bioorg Med Chem. 2010;18:3951-60 pubmed publisher
    ..Moreover, these compounds can be raised into a potential anti-inflammatory drug candidate after optimizing and passing several phases of clinical trials. ..
  26. Wu K, Kovacev J, Pan Z. Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for polyubiquitination on a SCF substrate. Mol Cell. 2010;37:784-96 pubmed publisher
  27. Zeng K, Fu H, Liu G, Wang X. Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-kappaB and JNK/p38 MAPK pathways. Int Immunopharmacol. 2010;10:668-78 pubmed publisher
  28. Jagielska J, Salguero G, Schieffer B, Bavendiek U. Digitoxin elicits anti-inflammatory and vasoprotective properties in endothelial cells: Therapeutic implications for the treatment of atherosclerosis?. Atherosclerosis. 2009;206:390-6 pubmed publisher
    ..These observations indicate a potential therapeutical application of digitoxin in the treatment of cardiovascular diseases, such as atherosclerosis. ..
  29. Gu X, Zhou L, Zhang M, Dai W, Chen S, He S, et al. Targeted NF-kappaB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model. Cell Immunol. 2009;260:14-20 pubmed publisher
    ..These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma. ..
  30. An Y, Xiao J, Jiang L, Yang X, Yu J, Zhao X. Clinical and molecular characterization of X-linked hyper-IgM syndrome patients in China. Scand J Immunol. 2010;72:50-6 pubmed publisher
    ..These mutations reflect the heterogeneity of CD40L gene, indicating the need for accurate and reliable molecular testing in patients suspected of XHIM. ..
  31. Lin W, Liang W, Lee Y, Chuang S, Tseng T. Antitumor progression potential of caffeic acid phenethyl ester involving p75(NTR) in C6 glioma cells. Chem Biol Interact. 2010;188:607-15 pubmed publisher
    ..In addition, histological examination of the mouse lung sections showed that the CAPE-treated group inhibited the metastasis of C6 glioma cells. These data suggest CAPE possesses antitumor progression potential. ..
  32. Cheng C, Chen Y, Chang W, Yang S, Chang D, Lai J, et al. Phytoestrogen bavachin mediates anti-inflammation targeting Ikappa B kinase-I kappaB alpha-NF-kappaB signaling pathway in chondrocytes in vitro. Eur J Pharmacol. 2010;636:181-8 pubmed publisher
    ..Our results suggest that through decreasing IL-1 beta-induced activation of IKK-I kappaB alpha-NF-kappaB signaling pathway, bavachin potentially protects cartilage from inflammation-mediated damage in joints of osteoarthritis patients. ..
  33. Allison D, Mayo M. StIKKing together: do multiple IKK pathways cooperate in the DNA-damage response?. Mol Cell. 2010;37:453-4 pubmed publisher
    ..2010) show that genotoxic stress requires SUMOylated IKKvarepsilon to regulate NF-kappaB transcription and cell survival. ..
  34. Mullen A, Loscher C, Roche H. Anti-inflammatory effects of EPA and DHA are dependent upon time and dose-response elements associated with LPS stimulation in THP-1-derived macrophages. J Nutr Biochem. 2010;21:444-50 pubmed publisher
    ..Immune responses are dynamic, and the present study suggests a nutrient sensitive window of LPS activation at which EPA and DHA are strongly anti-inflammatory. ..
  35. Lopez Guerra M, Colomer D. NF-kappaB as a therapeutic target in chronic lymphocytic leukemia. Expert Opin Ther Targets. 2010;14:275-88 pubmed publisher
    ..NF-kappaB is a relevant target in CLL and inhibitors of this prosurvival pathway, alone or in combination, represent a novel therapeutic strategy for the treatment of CLL patients. ..
  36. Eckmann L, Nebelsiek T, Fingerle A, Dann S, Mages J, Lang R, et al. Opposing functions of IKKbeta during acute and chronic intestinal inflammation. Proc Natl Acad Sci U S A. 2008;105:15058-63 pubmed publisher
    ..Our findings caution against the therapeutic use of IKKbeta/NF-kappaB inhibitors in acute inflammatory settings dominated by cell loss and ulceration. ..
  37. Xu G, Tan X, Wang H, Sun W, Shi Y, Burlingame S, et al. Ubiquitin-specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear factor kappaB activation via binding to and deubiquitinating receptor-interacting protein 1. J Biol Chem. 2010;285:969-78 pubmed publisher
    ..Therefore, our results demonstrate that USP21 plays an important role in the down-regulation of TNFalpha-induced NF-kappaB activation through deubiquitinating RIP1. ..
  38. Song L, Huang Q, Chen K, Liu L, Lin C, Dai T, et al. miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-?. Biochem Biophys Res Commun. 2010;402:135-40 pubmed publisher
    ..Taken together, our results suggest that miR-218 plays an important role in preventing the invasiveness of glioma cells, and our results present a novel mechanism of miRNA-mediated direct suppression of IKK-?/NF-?B pathway in gliomas. ..
  39. Bollrath J, Greten F. IKK/NF-kappaB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep. 2009;10:1314-9 pubmed publisher
    ..By contrast, in tumorigenic cells, both NF-kappaB and STAT3 control apoptosis, and STAT3 can also enhance proliferation. Consequently, inflammation should be considered as a valuable target for cancer prevention and therapy. ..
  40. Doyon P, Servant M. Tumor necrosis factor receptor-associated factor-6 and ribosomal S6 kinase intracellular pathways link the angiotensin II AT1 receptor to the phosphorylation and activation of the IkappaB kinase complex in vascular smooth muscle cells. J Biol Chem. 2010;285:30708-18 pubmed publisher
  41. Soden R, Botero T, Hanks C, Nor J. Angiogenic signaling triggered by cariogenic bacteria in pulp cells. J Dent Res. 2009;88:835-40 pubmed publisher
    ..Understanding signaling pathways triggered by cariogenic bacteria may reveal novel therapeutic targets for the clinical management of pulpitis. ..
  42. Bockhart V, Constantin C, Häussler A, Wijnvoord N, Kanngiesser M, Myrczek T, et al. Inhibitor kappaB Kinase beta deficiency in primary nociceptive neurons increases TRP channel sensitivity. J Neurosci. 2009;29:12919-29 pubmed publisher
    ..6 at NR. The results suggest that IKKbeta functions as a negative modulator of sensory neuron excitability, mediated at least in part by modulation of TRP channel sensitivity. ..
  43. Choi S, Kim F, Schwartz M, Wisse B. Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids. Am J Physiol Endocrinol Metab. 2010;298:E1122-30 pubmed publisher
    ..Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells. ..
  44. Sakamoto K, Hikiba Y, Nakagawa H, Hayakawa Y, Yanai A, Akanuma M, et al. Inhibitor of kappaB kinase beta regulates gastric carcinogenesis via interleukin-1alpha expression. Gastroenterology. 2010;139:226-38.e6 pubmed publisher
    ..17 +/- 0.44) than in control mice (2.42 +/- 0.52). IKKbeta regulates gastric carcinogenesis via IL-1alpha expression, which is associated with anti-apoptotic signaling and cell proliferation. ..
  45. Tsuchiya Y, Asano T, Nakayama K, Kato T, Karin M, Kamata H. Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation. Mol Cell. 2010;39:570-82 pubmed publisher
    ..NF-kappaB activated by the nuclear IKKbeta adaptor protein suppresses anti-apoptotic gene expression and promotes UV-induced cell death. ..
  46. Son P, Park S, Na H, Jue D, Kim S, Surh Y. Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF-{kappa}B activation and cyclooxygenase-2 expression in human breast epithelial cells: cysteine 179 of IKK{beta} as a potential target. Carcinogenesis. 2010;31:1442-9 pubmed publisher
  47. Yang L, Qian Z, Ji H, Yang R, Wang Y, Xi L, et al. Inhibitory effect on protein kinase Ctheta by Crocetin attenuates palmitate-induced insulin insensitivity in 3T3-L1 adipocytes. Eur J Pharmacol. 2010;642:47-55 pubmed publisher
    ..Taken together, Crocetin inhibited JNK and IKKbeta activation via suppression of PKCtheta phosphorylation, attenuating insulin insensitivity induced by palmitate in 3T3-L1 adipocytes. ..
  48. Wu J, Xu H, Yang M, Martin C, Kvietys P, Rui T. NADPH oxidase contributes to conversion of cardiac myocytes to a proinflammatory phenotype in sepsis. Free Radic Biol Med. 2009;46:1338-45 pubmed publisher
  49. Haybaeck J, Zeller N, Wolf M, Weber A, Wagner U, Kurrer M, et al. A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell. 2009;16:295-308 pubmed publisher
    ..Thus, sustained LT signaling represents a pathway involved in hepatitis-induced HCC. ..
  50. Gotoh K, Tanaka Y, Nishikimi A, Nakamura R, Yamada H, Maeda N, et al. Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. J Exp Med. 2010;207:721-30 pubmed publisher
    ..Owing to its hematopoietic cell-specific expression, DOCK2 may serve as a therapeutic target for type I IFN-related autoimmune diseases. ..
  51. Seo A, Hong S, Shin J, Park I, Hong N, Kim D, et al. Sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKKbeta. Apoptosis. 2009;14:913-22 pubmed publisher
    ..Together, these findings suggest that sulindac induces apoptosis in susceptible human breast cancer cells through, at least in part, the inhibition of IKKbeta and the subsequent p38 MAPK-dependent activation of JNK1. ..
  52. Paz S, Vilasco M, Arguello M, Sun Q, Lacoste J, Nguyen T, et al. Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon signaling adapter. Mol Cell Biol. 2009;29:3401-12 pubmed publisher
    ..These results provide further support for the differential role of IKKepsilon and TBK-1 in the RIG-I/Mda5 pathway. ..
  53. Gossye V, Elewaut D, Bougarne N, Bracke D, Van Calenbergh S, Haegeman G, et al. Differential mechanism of NF-kappaB inhibition by two glucocorticoid receptor modulators in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2009;60:3241-50 pubmed publisher
    ..A dual pathway, partially dependent and partially independent of GR (nongenomic), may explain the gene-inhibitory effects of CpdA in RA FLS. ..
  54. Philippe O, Rio M, Carioux A, Plaza J, Guigue P, Molinari F, et al. Combination of linkage mapping and microarray-expression analysis identifies NF-kappaB signaling defect as a cause of autosomal-recessive mental retardation. Am J Hum Genet. 2009;85:903-8 pubmed publisher
    ..Moreover, TNF-alpha stimulation assays showed a defect in IkBalpha degradation, suggesting impaired NF-kappaB signaling in patient cells. This study provides evidence of an NF-kappaB signaling defect in isolated MR. ..
  55. Gouin E, Adib Conquy M, Balestrino D, Nahori M, Villiers V, Colland F, et al. The Listeria monocytogenes InlC protein interferes with innate immune responses by targeting the I{kappa}B kinase subunit IKK{alpha}. Proc Natl Acad Sci U S A. 2010;107:17333-8 pubmed publisher
    ..Together, these results demonstrate that InlC, by interacting with IKK?, dampens the host innate response induced by Listeria during the infection process...
  56. Wu Z, Wong E, Shi Y, Niu J, Chen Z, Miyamoto S, et al. ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol Cell. 2010;40:75-86 pubmed publisher
    ..Thus, ATM- and NEMO-dependent ubiquitination of ELKS leads to the ubiquitin-dependent assembly of TAK1/TAB2/3 and NEMO/IKK complexes, resulting in IKK and NF-?B activation following genotoxic stimuli...
  57. Lahtela J, Nousiainen H, Stefanovic V, Tallila J, Viskari H, Karikoski R, et al. Mutant CHUK and severe fetal encasement malformation. N Engl J Med. 2010;363:1631-7 pubmed publisher
    ..CHUK has an essential role in the development of skin epidermis and its derivatives, along with various other morphogenetic events. (Funded by the Academy of Finland and others.). ..
  58. Bradley E, Drissi M. WNT5A regulates chondrocyte differentiation through differential use of the CaN/NFAT and IKK/NF-kappaB pathways. Mol Endocrinol. 2010;24:1581-93 pubmed publisher
    ..These data indicate that Wnt5a regulates chondrogenesis and chondrocyte hypertrophy in a stage-dependent manner through differential utilization of NFAT- and NF-kappaB-dependent signal transduction. ..
  59. Paszek P, Ryan S, Ashall L, Sillitoe K, Harper C, Spiller D, et al. Population robustness arising from cellular heterogeneity. Proc Natl Acad Sci U S A. 2010;107:11644-9 pubmed publisher
    ..Our analyses suggest in contrast, that this cellular variation might be advantageous and subject to evolutionary selection. Alternative types of therapy could perhaps be designed to modulate this cellular heterogeneity. ..
  60. Liu H, Chen A, Guo F, Yuan L. A short-hairpin RNA targeting osteopontin downregulates MMP-2 and MMP-9 expressions in prostate cancer PC-3 cells. Cancer Lett. 2010;295:27-37 pubmed publisher
  61. Emmanouil M, Taoufik E, Tseveleki V, Vamvakas S, Tselios T, Karin M, et al. Neuronal I kappa B kinase beta protects mice from autoimmune encephalomyelitis by mediating neuroprotective and immunosuppressive effects in the central nervous system. J Immunol. 2009;183:7877-89 pubmed publisher
  62. Witt J, Barisic S, Schumann E, Allgöwer F, Sawodny O, Sauter T, et al. Mechanism of PP2A-mediated IKK beta dephosphorylation: a systems biological approach. BMC Syst Biol. 2009;3:71 pubmed publisher
    ..The evidence of constitutive activity of PP2Ac at the IKK complex provides new insights into the feedback regulation of NF kappa B, which is crucial for the development of new anti-cancer strategies. ..