Ikbkb

Summary

Gene Symbol: Ikbkb
Description: inhibitor of nuclear factor kappa B kinase subunit beta
Alias: AIM-1, IKK2, inhibitor of nuclear factor kappa-B kinase subunit beta, I-kappa-B kinase 2, I-kappa-B-kinase beta, IKK-B, IKK-beta, NFKBIKB, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta, inhibitor of kappaB kinase beta, inhibitor of nuclear factor kappa B kinase beta subunit, nuclear factor NF-kappa-B inhibitor kinase beta
Species: rat
Products:     Ikbkb

Top Publications

  1. Pasparakis M, Courtois G, Hafner M, Schmidt Supprian M, Nenci A, Toksoy A, et al. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature. 2002;417:861-6 pubmed
    The I kappa B kinase (IKK), consisting of the IKK1 and IKK2 catalytic subunits and the NEMO (also known as IKK gamma) regulatory subunit, phosphorylates I kappa B proteins, targeting them for degradation and thus inducing activation of NF-..
  2. 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. ..
  3. Xu G, Lo Y, Li Q, Napolitano G, Wu X, Jiang X, et al. Crystal structure of inhibitor of ?B kinase ?. Nature. 2011;472:325-30 pubmed publisher
    ..Other IKK family members, IKK?, TBK1 and IKK-i, may have a similar trimodular architecture and function...
  4. Watterson S, Langevine C, Van Kirk K, Kempson J, Guo J, Spergel S, et al. Novel tricyclic inhibitors of IKK2: discovery and SAR leading to the identification of 2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl)pyridin-2-yl)methyl)acetamide (BMS-066). Bioorg Med Chem Lett. 2011;21:7006-12 pubmed publisher
    ..relationships (SAR), and biological results of pyridyl-substituted azaindole based tricyclic inhibitors of IKK2 are described...
  5. Yaspelkis B, Kvasha I, Figueroa T. High-fat feeding increases insulin receptor and IRS-1 coimmunoprecipitation with SOCS-3, IKKalpha/beta phosphorylation and decreases PI-3 kinase activity in muscle. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1709-15 pubmed publisher
  6. Qin W, Luo Y, Yu C. [Influence of electroacupuncture intervention on hippocampal IL-1beta content and I kappa B kinase beta expression in focal cerebral ischemia/reperfusion rats]. Zhen Ci Yan Jiu. 2013;38:271-6 pubmed
  7. Polley S, Huang D, Hauenstein A, Fusco A, Zhong X, Vu D, et al. A structural basis for I?B kinase 2 activation via oligomerization-dependent trans auto-phosphorylation. PLoS Biol. 2013;11:e1001581 pubmed publisher
    ..Here we report a 4 Å x-ray crystal structure of human IKK2 (hIKK2) in its catalytically active conformation...
  8. Meng Q, Lou F, Hou W, Liu M, Guo H, Zhang X. Acetylpuerarin reduces inflammation and improves memory function in a rat model of Alzheimer's disease induced by Abeta1-42. Pharmazie. 2013;68:904-8 pubmed
    ..Acetylpuerarin improves learning and memory functions in Abeta1-42 induced rat models. These effects may be due to anti-neuroinflammatory effects. ..
  9. Tai D, Su C, Ma Y, Lee E. SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression. J Biol Chem. 2009;284:4073-89 pubmed publisher
    ..Our results together demonstrated novel substrate proteins of SGK1 and novel SGK1 signaling pathways. Activation of these signaling pathways enhances NR2A and NR2B expression that is implicated in neuronal plasticity. ..

More Information

Publications78

  1. Hu W, Pendergast J, Mo X, Brambilla R, Bracchi Ricard V, Li F, et al. NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation. J Biol Chem. 2005;280:29233-41 pubmed
    ..Because of its neuronal expression, we propose that NIBP may be a potential target for modulating the NF-(kappa)B signaling cascade in neuronal pathologies dependent upon abnormal activation of this pathway. ..
  2. Gillooly K, Pattoli M, Taylor T, Chen L, Cheng L, Gregor K, et al. Periodic, partial inhibition of IkappaB Kinase beta-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis. J Pharmacol Exp Ther. 2009;331:349-60 pubmed publisher
    ..Thus, only partial and transient inhibition of IKKbeta is sufficient to yield dramatic benefit in vivo, and this understanding will be important in the clinical development of IKKbeta inhibitors. ..
  3. Slattery M, John E, Torres Mejía G, Lundgreen A, Herrick J, Baumgartner K, et al. Genetic variation in genes involved in hormones, inflammation and energetic factors and breast cancer risk in an admixed population. Carcinogenesis. 2012;33:1512-21 pubmed publisher
    ..Within admixture strata, breast cancer risk among women with low Native American ancestry was associated with IkBKB, NF?B1, PTEN and RPS6KA2, whereas among women with high Native American ancestry, breast cancer risk was ..
  4. Cheng J, Wu C, Gotlinger K, Zhang F, Falck J, Narsimhaswamy D, et al. 20-hydroxy-5,8,11,14-eicosatetraenoic acid mediates endothelial dysfunction via IkappaB kinase-dependent endothelial nitric-oxide synthase uncoupling. J Pharmacol Exp Ther. 2010;332:57-65 pubmed publisher
    ..The results indicate that 20-HETE mediates eNOS uncoupling and endothelial dysfunction via the activation of tyrosine kinase, MAPK, and IKK, and these effects are linked to 20-HETE-mediated endothelial activation. ..
  5. Kang Y, Ma Y, Zheng J, Elks C, Sriramula S, Yang Z, et al. Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension. Cardiovasc Res. 2009;82:503-12 pubmed publisher
    ..The increased superoxide in the PVN contributes to NF-kappaB activation and neurohumoral excitation in hypertension. ..
  6. Liu H, Fang D, Yue H, Deng H, Meng B, Wen Z, et al. [The effect of smoking and smoking cessation on the phosphorylation of IKK-ß in type 2 diabetic rats]. Zhonghua Nei Ke Za Zhi. 2010;49:426-8 pubmed
    ..After smoking cessation, the phosphorylation of IKK-ß decreased. The phosphorylation of IKK-ß may be involved in the mechanism by which smoking causes type 2 diabetes. ..
  7. Tanabe K, Nishimura K, Dohi S, Kozawa O. Mechanisms of interleukin-1beta-induced GDNF release from rat glioma cells. Brain Res. 2009;1274:11-20 pubmed publisher
    ..These results strongly suggest that IL-1beta stimulates GDNF release through the pathways of IkappaB-nuclear factor kappa B, p38 MAP kinase, p44/p42 MAP kinase and JAK-STAT3, but not through the SAPK/JNK pathway in glioma cells. ..
  8. Kupfer R, Scheinman R. Measurement of IKK activity in primary rat T cells: rapid activation and inactivation. J Immunol Methods. 2002;266:155-64 pubmed
  9. Je J, Lee J, Jung K, Sung B, Go E, Yu B, et al. NF-kappaB activation mechanism of 4-hydroxyhexenal via NIK/IKK and p38 MAPK pathway. FEBS Lett. 2004;566:183-9 pubmed
    ..These findings strongly suggest that HHE induces NF-kappaB activation through IKK/NIK pathway and/or p38 MAPK and ERK activation associated with oxidative stress in endothelial cells. ..
  10. Suzuki K, Verma I. Phosphorylation of SNAP-23 by IkappaB kinase 2 regulates mast cell degranulation. Cell. 2008;134:485-95 pubmed publisher
    ..Upon FcvarepsilonRI stimulation, IKK2 phosphorylates SNAP-23, the target membrane soluble N-ethylmaleimide-sensitive fusion factor attachment protein ..
  11. Zolotnik I, Figueroa T, Yaspelkis B. Insulin receptor and IRS-1 co-immunoprecipitation with SOCS-3, and IKK?/? phosphorylation are increased in obese Zucker rat skeletal muscle. Life Sci. 2012;91:816-22 pubmed publisher
    ..These two mechanisms thusly may independently contribute to impairing insulin-stimulated PI3-K activation in the skeletal muscle of the obese Zucker rat. ..
  12. Kumar S, Chakraborty S, Barbosa C, Brustovetsky T, Brustovetsky N, Obukhov A. Mechanisms controlling neurite outgrowth in a pheochromocytoma cell line: the role of TRPC channels. J Cell Physiol. 2012;227:1408-19 pubmed publisher
  13. Xie W, Zhang L, Jiao H, Guan L, Zha J, Li X, et al. Chaperone-mediated autophagy prevents apoptosis by degrading BBC3/PUMA. Autophagy. 2015;11:1623-35 pubmed publisher
    ..We further demonstrate that upon TNF (tumor necrosis factor) treatment, IKBKB/IKKβ (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase β)-mediated BBC3 Ser10 ..
  14. Müller Rischart A, Pilsl A, Beaudette P, Patra M, Hadian K, Funke M, et al. The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Mol Cell. 2013;49:908-21 pubmed publisher
  15. Clark P, Kim R, Pober J, Kluger M. Tumor necrosis factor disrupts claudin-5 endothelial tight junction barriers in two distinct NF-κB-dependent phases. PLoS ONE. 2015;10:e0120075 pubmed publisher
    ..We conclude that TNF disrupts TJs in HDMECs in two distinct NF-κB-dependent steps, the first involving Rho-associated kinase and the second likely to involve an as yet unidentified but structurally related protein kinase(s). ..
  16. Cui J, Zhu L, Xia X, Wang H, Legras X, Hong J, et al. NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell. 2010;141:483-96 pubmed publisher
    ..Our findings identify NLRC5 as a negative regulator that blocks two central components of the NF-kappaB and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity. ..
  17. Yin W, Yang J, Hu X, Yuan J, Luo Y, Li Y. [Effects of polymixin B on I-kappaB kinase mRNA expression in lipopolysaccharide- induced pulmonary alveolar macrophages]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2003;15:429-31 pubmed
  18. Gupte A, Bomhoff G, Morris J, Gorres B, Geiger P. Lipoic acid increases heat shock protein expression and inhibits stress kinase activation to improve insulin signaling in skeletal muscle from high-fat-fed rats. J Appl Physiol (1985). 2009;106:1425-34 pubmed publisher
    ..In conclusion, our results suggest chronic LA treatment results in stress kinase inhibition and improved insulin signaling through a HSP-mediated mechanism. ..
  19. Wooten M, Geetha T, Seibenhener M, Babu J, Diaz Meco M, Moscat J. The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination. J Biol Chem. 2005;280:35625-9 pubmed
    ..These results provide evidence for a mechanism whereby p62 serves to regulate the NF-kappaB pathway. ..
  20. Cai D, Yuan M, Frantz D, Melendez P, Hansen L, Lee J, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183-90 pubmed
    ..This causes insulin resistance both locally in liver and systemically. ..
  21. Zhang Y, Lapidus R, Liu P, Choi E, Adediran S, Hussain A, et al. Targeting I?B Kinase ?/NF-?B Signaling in Human Prostate Cancer by a Novel I?B Kinase ? Inhibitor CmpdA. Mol Cancer Ther. 2016;15:1504-14 pubmed publisher
    ..Mol Cancer Ther; 15(7); 1504-14. ©2016 AACR. ..
  22. Gupte A, Bomhoff G, Swerdlow R, Geiger P. Heat treatment improves glucose tolerance and prevents skeletal muscle insulin resistance in rats fed a high-fat diet. Diabetes. 2009;58:567-78 pubmed publisher
  23. Bruno M, Borchers C, Dial J, Walker N, Hartis J, Wetmore B, et al. Effects of TCDD upon IkappaB and IKK subunits localized in microsomes by proteomics. Arch Biochem Biophys. 2002;406:153-64 pubmed
    ..xenobiotic metabolism enzymes as well as a protein at 90kDa identified by mass spectrometry as IkappaB kinase beta/IKK2. This observation led to the discovery of other NF-kappaB binding proteins and kinases in microsomes and effects by ..
  24. Lu H, Lu Q, Gaddipati S, Kasetti R, Wang W, Pasparakis M, et al. IKK2 inhibition attenuates laser-induced choroidal neovascularization. PLoS ONE. 2014;9:e87530 pubmed publisher
    ..Inflammation has been suggested as a risk factor for AMD. The IKK2/NF-?B pathway plays a key role in the inflammatory response through regulation of the transcription of cytokines, ..
  25. Azoitei N, Wirth T, Baumann B. Activation of the IkappaB kinase complex is sufficient for neuronal differentiation of PC12 cells. J Neurochem. 2005;93:1487-501 pubmed
    ..Ectopic expression of a constitutively active form of IKK2 but not of IKK1 promoted neurite outgrowth in the absence of NGF...
  26. Page A, Navarro M, Garin M, Perez P, Casanova M, Moreno R, et al. IKKbeta leads to an inflammatory skin disease resembling interface dermatitis. J Invest Dermatol. 2010;130:1598-610 pubmed publisher
    ..Our results also support the idea that IKKbeta might be a valid therapeutic target for the treatment of skin inflammatory diseases. ..
  27. Rajendrasozhan S, Hwang J, Yao H, Kishore N, Rahman I. Anti-inflammatory effect of a selective IkappaB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke. Pulm Pharmacol Ther. 2010;23:172-81 pubmed publisher
    ..We investigated the anti-inflammatory effect of a highly selective and novel IKKbeta/IKK2 inhibitor, PHA-408 [8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[..
  28. Edinger R, Lebowitz J, Li H, Alzamora R, Wang H, Johnson J, et al. Functional regulation of the epithelial Na+ channel by IkappaB kinase-beta occurs via phosphorylation of the ubiquitin ligase Nedd4-2. J Biol Chem. 2009;284:150-7 pubmed publisher
    ..In summary, these results suggest a novel mode of ENaC regulation that occurs through IKKbeta-dependent Nedd4-2 phosphorylation at a recognized SGK1 and protein kinase A target site. ..
  29. Van Gammeren D, Damrauer J, Jackman R, Kandarian S. The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy. FASEB J. 2009;23:362-70 pubmed publisher
    ..These data show that both IKKalpha and IKKbeta are necessary and sufficient for physiological muscle atrophy. ..
  30. Slomiany B, Slomiany A. Induction in gastric mucosal prostaglandin and nitric oxide by Helicobacter pylori is dependent on MAPK/ERK-mediated activation of IKK-? and cPLA2: modulatory effect of ghrelin. Inflammopharmacology. 2013;21:241-51 pubmed publisher
  31. Wang W, Guo M, Hu L, Cai J, Zeng Y, Luo J, et al. The zinc finger protein ZNF268 is overexpressed in human cervical cancer and contributes to tumorigenesis via enhancing NF-?B signaling. J Biol Chem. 2012;287:42856-66 pubmed publisher
    ..Taken together, our results reveal a novel role of ZNF268b2 that contributes to cervical carcinogenesis in part through enhancing NF-?B signaling. ..
  32. Chang N. The non-ankyrin C terminus of Ikappa Balpha physically interacts with p53 in vivo and dissociates in response to apoptotic stress, hypoxia, DNA damage, and transforming growth factor-beta 1-mediated growth suppression. J Biol Chem. 2002;277:10323-31 pubmed
    ..Together, the IkappaBalpha x p53 complex plays an important role in responses involving growth regulation, apoptosis, and hypoxic stress. ..
  33. Yang J, Zaja Milatovic S, Thu Y, Lee F, Smykla R, Richmond A. Molecular determinants of melanoma malignancy: selecting targets for improved efficacy of chemotherapy. Mol Cancer Ther. 2009;8:636-47 pubmed publisher
    ..In contrast, drug targeting of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway alone in melanoma cells is ineffective for melanoma therapy in cases where NF-kappaB is not also targeted. ..
  34. Wu L, Iwai M, Li Z, Li J, Mogi M, Horiuchi M. Nifedipine inhibited angiotensin II-induced monocyte chemoattractant protein 1 expression: involvement of inhibitor of nuclear factor kappa B kinase and nuclear factor kappa B-inducing kinase. J Hypertens. 2006;24:123-30 pubmed
    ..As NIK is reported to activate IKK, our results suggest that nifedipine attenuates the effect of Ang II on MCP-1 expression in VSMC by regulating the activity of NF-kappaB through NIK, IKK and IkappaB. ..
  35. Grassia G, Maddaluno M, Musilli C, De Stefano D, Carnuccio R, Di Lauro M, et al. The I{kappa}B kinase inhibitor nuclear factor-{kappa}B essential modulator-binding domain peptide for inhibition of injury-induced neointimal formation. Arterioscler Thromb Vasc Biol. 2010;30:2458-66 pubmed publisher
    ..The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation...
  36. Levrand S, Pesse B, Feihl F, Waeber B, Pacher P, Rolli J, et al. Peroxynitrite is a potent inhibitor of NF-{kappa}B activation triggered by inflammatory stimuli in cardiac and endothelial cell lines. J Biol Chem. 2005;280:34878-87 pubmed
    ..These findings offer new perspectives for the understanding of the relationships between redox stress and inflammation. ..
  37. Ho R, Hirshman M, Li Y, Cai D, Farmer J, Aschenbach W, et al. Regulation of IkappaB kinase and NF-kappaB in contracting adult rat skeletal muscle. Am J Physiol Cell Physiol. 2005;289:C794-801 pubmed
    ..In conclusion, acute submaximal exercise transiently stimulates NF-kappaB signaling in skeletal muscle. This activation is a local event because it can occur in the absence of exercise-derived systemic factors. ..
  38. Zhao C, Wang Y, Zhou J, Jia B, Cui J. [An experimental study on the reverse mechanism of PPAR-gamma agonist rosiglitazone in rats with non-alcoholic steatohepatitis]. Zhonghua Gan Zang Bing Za Zhi. 2007;15:450-5 pubmed
    ..This may help to provide a new idea for treating NASH effectively. ..
  39. Chen X, Liu X, Wan X, Wu Y, Chen Y, Cao C. Ischemic preconditioning attenuates renal ischemia-reperfusion injury by inhibiting activation of IKKbeta and inflammatory response. Am J Nephrol. 2009;30:287-94 pubmed publisher
    ..It appears that IPC may attenuate renal injury and the expression of NGAL following acute I/R injury. IKKbeta may offer a clinically accessible target for preventing renal injury following I/R. ..
  40. Aiello S, Cassis P, Cassis L, Tomasoni S, Benigni A, Pezzotta A, et al. DnIKK2-transfected dendritic cells induce a novel population of inducible nitric oxide synthase-expressing CD4+CD25- cells with tolerogenic properties. Transplantation. 2007;83:474-84 pubmed
    ..rat bone marrow-derived dendritic cells (DCs), transfected with an adenovirus encoding a dominant negative form of IKK2 (dnIKK2), have impaired allostimulatory capacity and generate CD4 T cells with regulatory function...
  41. Shukla S, Kanwal R, Shankar E, Datt M, Chance M, Fu P, et al. Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget. 2015;6:31216-32 pubmed publisher
    ..Overall, our results suggest that inhibition of cell proliferation, invasiveness and decrease in tumor growth by apigenin are mediated by its ability to suppress IKKα and downstream targets affecting NF-ĸB signaling pathways. ..
  42. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45-65 pubmed
    ..In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed. ..
  43. Doyon P, van Zuylen W, Servant M. Role of I?B kinase-? in the growth-promoting effects of angiotensin II in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2013;33:2850-7 pubmed publisher
    ..Our findings provide new insights into the molecular understanding of the pathological role of Ang II and assist in identifying the beneficial effects of IKK? inhibition for the treatment of cardiovascular diseases. ..
  44. Romagnoli M, Gomez Cabrera M, Perrelli M, Biasi F, Pallardo F, Sastre J, et al. Xanthine oxidase-induced oxidative stress causes activation of NF-kappaB and inflammation in the liver of type I diabetic rats. Free Radic Biol Med. 2010;49:171-7 pubmed publisher
    ..Moreover, we found a significant neutrophil infiltration in the liver of diabetic animals. These events were also prevented by administration of allopurinol. ..
  45. Zhang B, Wang D, Ji T, Shi L, Yu J. Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-?B signaling pathway in a rat model. Oncotarget. 2017;8:17347-17359 pubmed publisher
    ..Overexpressed lncRNA ANRIL upregulates VEGF and promotes angiogenesis by activating NF-?B signaling pathway in DM + CI rats. . ..
  46. Pasparakis M, Schmidt Supprian M, Rajewsky K. IkappaB kinase signaling is essential for maintenance of mature B cells. J Exp Med. 2002;196:743-52 pubmed
    ..Activation of NF-kappaB is mediated by the IkappaB kinase (IKK) complex, which is composed of two kinases, IKK1 and IKK2, and a regulatory subunit termed NF-kappaB essential modulator (NEMO)...
  47. Bernier M, Kwon Y, Pandey S, Zhu T, Zhao R, Maciuk A, et al. Binding of manumycin A inhibits IkappaB kinase beta activity. J Biol Chem. 2006;281:2551-61 pubmed
    ..Thus, manumycin A with its epoxyquinoid moieties plays an important regulatory function in IKK signaling through pathways distinct from its role as a protein farnesylation inhibitor. ..
  48. Herrmann O, Baumann B, De Lorenzi R, Muhammad S, Zhang W, Kleesiek J, et al. IKK mediates ischemia-induced neuronal death. Nat Med. 2005;11:1322-9 pubmed
    ..To investigate the function of IKK in brain ischemia we generated mice that contain a targeted deletion of Ikbkb (which encodes IKK2) in mouse neurons and mice that express a dominant inhibitor of IKK in neurons...
  49. Ouyang J, Fan C, Wen D, Hou J, Du Y, Wang Y, et al. Donor antigen-loaded IKK2dn gene-modified dendritic cells prolong allograft survival. Scand J Immunol. 2010;71:336-44 pubmed publisher
    ..Previous studies demonstrated that blocking IKK2 in bone marrow-derived dendritic cells (BMDC) by adenoviral transfection with a kinase-defective dominant negative ..
  50. Schopf L, Savinainen A, Anderson K, Kujawa J, DuPont M, Silva M, et al. IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis. Arthritis Rheum. 2006;54:3163-73 pubmed
    ..Methods for the determination of serum markers for bone and cartilage destruction, as well as micro-CT analysis, may aid in predicting and evaluating the therapeutic efficacy of IKKbeta inhibition therapy in humans. ..
  51. Zhang Y, Sun S, Chen W, Kaluzhny Y, Chinnappan D, Yu G, et al. Repression of AIM-1 kinase mRNA as part of a program of genes regulated by Mpl ligand. Biochem Biophys Res Commun. 2001;282:844-9 pubmed
    ..These data point to the potential importance of the transcriptional regulation of the AIM-1 gene for promoting megakaryocyte polyploidization. ..
  52. Dyckman A, Langevine C, Quesnelle C, Kempson J, Guo J, Gill P, et al. Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: synthesis, SAR, PK/PD and activity in a preclinical model of rheumatoid arthritis. Bioorg Med Chem Lett. 2011;21:383-6 pubmed publisher
    The synthesis, structure-activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be orally efficacious in a murine model of rheumatoid arthritis.
  53. Nemoto S, DiDonato J, Lin A. Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. Mol Cell Biol. 1998;18:7336-43 pubmed
    ..The formation of the MEKK1-IKK complex versus the NIK-IKK complex may provide a molecular basis for regulation of the IKK complex by various extracellular signals. ..
  54. Makowski L, Brittingham K, Reynolds J, Suttles J, Hotamisligil G. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor gamma and IkappaB kinase activities. J Biol Chem. 2005;280:12888-95 pubmed
    ..Our results demonstrate that aP2 regulates two central molecular pathways to coordinate macrophage cholesterol trafficking and inflammatory activity. ..
  55. Jia R, Zhu J, Wu J, Xie J, Xu L. Experimental study on early protective effect of ischemic preconditioning on rat kidney graft. Transplant Proc. 2009;41:69-72 pubmed publisher
    ..The inhibiting effects on TNF-alpha and the positive feedback signaling of TNF-alpha/NF-KB pathways may play important roles in renal graft protection. ..
  56. Stratis A, Pasparakis M, Markur D, Knaup R, Pofahl R, Metzger D, et al. Localized inflammatory skin disease following inducible ablation of I kappa B kinase 2 in murine epidermis. J Invest Dermatol. 2006;126:614-20 pubmed
    ..Using mice with conditionally targeted I kappa B kinase 2 (IKK2) alleles, we have previously shown that epidermal keratinocytes can play a dominant role in the ..
  57. Bu D, Erl W, de Martin R, Hansson G, Yan Z. IKKbeta-dependent NF-kappaB pathway controls vascular inflammation and intimal hyperplasia. FASEB J. 2005;19:1293-5 pubmed
    ..Collectively, these findings show that the IKKbeta-mediated late-phase NF-kappaB activation contributes to intimal hyperplasia and the accompanied vascular inflammatory responses. ..
  58. Hayes J, Dinkova Kostova A. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39:199-218 pubmed publisher
  59. Masaki M, Ikeda A, Shiraki E, Oka S, Kawasaki T. Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically. Eur J Biochem. 2003;270:76-83 pubmed
    ..We also provided evidence that LZK was associated directly with the IKK complex through the kinase domain, and that AOP-1 was recruited to the IKK complex through the binding to LZK. ..
  60. Karim Z, Zhang J, Banerjee M, Chicka M, Al Hawas R, Hamilton T, et al. I?B kinase phosphorylation of SNAP-23 controls platelet secretion. Blood. 2013;121:4567-74 pubmed publisher
    ..In vivo studies with IKK inhibitors or platelet-specific IKK-? knockout mice showed that blocking IKK-? activity significantly prolonged tail bleeding times, suggesting that currently available IKK inhibitors may affect hemostasis. ..
  61. Fillmann H, Kretzmann N, San Miguel B, Llesuy S, Marroni N, Gonzalez Gallego J, et al. Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat. Toxicology. 2007;236:217-26 pubmed
  62. Jain S, Bird R. Elevated expression of tumor necrosis factor-alpha signaling molecules in colonic tumors of Zucker obese (fa/fa) rats. Int J Cancer. 2010;127:2042-50 pubmed publisher
    ..It is concluded that the physiological state of the host intricately affects tumor phenotype. ..
  63. Lamkanfi M, Denecker G, Kalai M, D hondt K, Meeus A, Declercq W, et al. INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1beta generation. J Biol Chem. 2004;279:51729-38 pubmed
    ..Our data show that INCA is a novel intracellular regulator of procaspase-1 activation, involved in the regulation of pro-IL-1beta processing and its release during inflammation. ..
  64. Hu M, Lee D, Xia W, Golfman L, Ou Yang F, Yang J, et al. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell. 2004;117:225-37 pubmed
    ..These results suggest the negative regulation of FOXO factors by IKK as a key mechanism for promoting cell growth and tumorigenesis. ..
  65. Tang J, Michaelis K, Nozik Grayck E, Seedorf G, Hartman Filson M, Abman S, et al. The NF-?B inhibitory proteins I?B? and I?B? mediate disparate responses to inflammation in fetal pulmonary endothelial cells. J Immunol. 2013;190:2913-23 pubmed publisher
  66. Baumann B, Wagner M, Aleksic T, von Wichert G, Weber C, Adler G, et al. Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo. J Clin Invest. 2007;117:1502-13 pubmed
    ..gene under the control of the rat elastase promoter were generated to mediate acinar cell-specific expression of IKK2 alleles...
  67. Fontan E, Traincard F, Levy S, Yamaoka S, Veron M, Agou F. NEMO oligomerization in the dynamic assembly of the IkappaB kinase core complex. FEBS J. 2007;274:2540-51 pubmed
  68. Bikman B, Woodlief T, Noland R, Britton S, Koch L, Lust R, et al. High-fat diet induces Ikkbeta and reduces insulin sensitivity in rats with low running capacity. Int J Sports Med. 2009;30:631-5 pubmed publisher
    ..IRS-1 pSer (307) in the LCR rats increased on the HFD vs. chow. We conclude that differences in glucose tolerance between LCR and HCR rats are at least partly explained by differences in IKKbeta activity and pSer (307) levels. ..
  69. Wan F, Weaver A, Gao X, Bern M, Hardwidge P, Lenardo M. IKK? phosphorylation regulates RPS3 nuclear translocation and NF-?B function during infection with Escherichia coli strain O157:H7. Nat Immunol. 2011;12:335-43 pubmed publisher
    ..Thus, the IKK?-dependent modification of a specific amino acid in RPS3 promoted specific NF-?B functions that underlie the molecular pathogenetic mechanisms of E. coli O157:H7. ..