The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Nfkbia  -  nuclear factor of kappa light polypeptide...

Mus musculus

Synonyms: AI462015, I(Kappa)B(alpha), I-kappa-B-alpha, I-kappaBalpha, IkB-alpha, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Nfkbia


High impact information on Nfkbia

  • In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-kappaB through expression of IkappaBalpha superrepressor (MISR) [6].
  • Growth arrest triggered by oncogenic Ras can be bypassed by IkappaBalpha-mediated blockade of NF-kappaB, generating malignant human epidermal tissue resembling squamous cell carcinoma [7].
  • Here, we directed a degradation-resistant IkappaBalpha transgene to mouse hepatocytes in an inducible manner and showed substantial tissue specificity using various means, including a new method for live-animal imaging [8].
  • The subsequent molecular events that regulate the termination of nuclear NF-kappaB action remain poorly defined, although the activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a key role [9].
  • This deacetylation reaction promotes effective binding to IkappaBalpha and leads in turn to IkappaBalpha-dependent nuclear export of the complex through a chromosomal region maintenance-1 (CRM-1)-dependent pathway [9].

Chemical compound and disease context of Nfkbia


Biological context of Nfkbia

  • The sensitivity and kinetics of TNF-alpha-induced apoptosis are shown to be enhanced in a number of cell types expressing a dominant-negative IkappaBalpha (IkappaBalphaM) [15].
  • Activation of nuclear factor-kappaB by core and NS3 was associated with increased IkappaBalpha phosphorylation [16].
  • Recruitment of IKKs to the nucleus in response to TNF-alpha may induce chromatin-associated IkappaBalpha release and gene activation [17].
  • Acetylation at lysines 218, 221, and 310 differentially regulates RelA's DNA binding activity, assembly with IkappaBalpha, and transcriptional activity [18].
  • We found a distinct consensus sequence within this domain of IkappaBalpha for PIR degradation [19].

Anatomical context of Nfkbia


Associations of Nfkbia with chemical compounds


Enzymatic interactions of Nfkbia


Regulatory relationships of Nfkbia

  • We hypothesize that IKK1 plays a checkpoint role in the proper control of IkappaBalpha kinase activity in innate and adaptive immunity [31].
  • The delayed restoration of IkappaBalpha in pathogen-activated IKK1-/- ELDM was a direct consequence of uncontrolled IKK2 kinase activity [31].
  • The effect on nuclear factor-kappaB (NF-kappaB) activation correlated with RANKL-induced IkappaBalpha kinase activation [32].
  • The sequential engagement of two distinct pathways, coupled with the negative feedback inhibition of RelA complexes by NF-kappaB-induced resynthesis of IkappaBalpha, resulted in a pronounced temporal change in the nature of the NF-kappaB activity during the course of stimulation [33].
  • Furthermore, the production of super-repressor IkappaBalpha suppressed the increase in blood glucose level after pyruvate injection [3].

Other interactions of Nfkbia


Analytical, diagnostic and therapeutic context of Nfkbia


  1. IkappaBalpha deficiency results in a sustained NF-kappaB response and severe widespread dermatitis in mice. Klement, J.F., Rice, N.R., Car, B.D., Abbondanzo, S.J., Powers, G.D., Bhatt, P.H., Chen, C.H., Rosen, C.A., Stewart, C.L. Mol. Cell. Biol. (1996) [Pubmed]
  2. Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. Duffey, D.C., Chen, Z., Dong, G., Ondrey, F.G., Wolf, J.S., Brown, K., Siebenlist, U., Van Waes, C. Cancer Res. (1999) [Pubmed]
  3. Amelioration of glucose tolerance by hepatic inhibition of nuclear factor kappaB in db/db mice. Tamura, Y., Ogihara, T., Uchida, T., Ikeda, F., Kumashiro, N., Nomiyama, T., Sato, F., Hirose, T., Tanaka, Y., Mochizuki, H., Kawamori, R., Watada, H. Diabetologia (2007) [Pubmed]
  4. Neuronal activity and transcription of proinflammatory cytokines, IkappaBalpha, and iNOS in the mouse brain during acute endotoxemia and chronic infection with Trypanosoma brucei brucei. Brochu, S., Olivier, M., Rivest, S. J. Neurosci. Res. (1999) [Pubmed]
  5. Evidence for a phosphorylation-independent role for Ser 32 and 36 in proteasome inhibitor-resistant (PIR) IkappaBalpha degradation in B cells. O'Connor, S., Markovina, S., Miyamoto, S. Exp. Cell Res. (2005) [Pubmed]
  6. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cai, D., Frantz, J.D., Tawa, N.E., Melendez, P.A., Oh, B.C., Lidov, H.G., Hasselgren, P.O., Frontera, W.R., Lee, J., Glass, D.J., Shoelson, S.E. Cell (2004) [Pubmed]
  7. NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Dajee, M., Lazarov, M., Zhang, J.Y., Cai, T., Green, C.L., Russell, A.J., Marinkovich, M.P., Tao, S., Lin, Q., Kubo, Y., Khavari, P.A. Nature (2003) [Pubmed]
  8. High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-kappaB activation. Lavon, I., Goldberg, I., Amit, S., Landsman, L., Jung, S., Tsuberi, B.Z., Barshack, I., Kopolovic, J., Galun, E., Bujard, H., Ben-Neriah, Y. Nat. Med. (2000) [Pubmed]
  9. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Chen Lf, n.u.l.l., Fischle, W., Verdin, E., Greene, W.C. Science (2001) [Pubmed]
  10. Adenoviral gene transfer of ABIN-1 protects mice from TNF/galactosamine-induced acute liver failure and lethality. Wullaert, A., Wielockx, B., Van Huffel, S., Bogaert, V., De Geest, B., Papeleu, P., Schotte, P., El Bakkouri, K., Heyninck, K., Libert, C., Beyaert, R. Hepatology (2005) [Pubmed]
  11. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Aggarwal, B.B., Shishodia, S., Takada, Y., Banerjee, S., Newman, R.A., Bueso-Ramos, C.E., Price, J.E. Clin. Cancer Res. (2005) [Pubmed]
  12. The inhibitor of I kappa B alpha phosphorylation BAY 11-7082 prevents NMDA neurotoxicity in mouse hippocampal slices. Goffi, F., Boroni, F., Benarese, M., Sarnico, I., Benetti, A., Spano, P.F., Pizzi, M. Neurosci. Lett. (2005) [Pubmed]
  13. Combination gene therapy for glioblastoma involving herpes simplex virus vector-mediated codelivery of mutant IkappaBalpha and HSV thymidine kinase. Moriuchi, S., Glorioso, J.C., Maruno, M., Izumoto, S., Wolfe, D., Huang, S., Cohen, J.B., Yoshimine, T. Cancer Gene Ther. (2005) [Pubmed]
  14. Hepatic expression of S32A/S36A IkappaBalpha does not reduce postischemic liver injury. Okaya, T., Lentsch, A.B. J. Surg. Res. (2005) [Pubmed]
  15. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Van Antwerp, D.J., Martin, S.J., Kafri, T., Green, D.R., Verma, I.M. Science (1996) [Pubmed]
  16. Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Dolganiuc, A., Oak, S., Kodys, K., Golenbock, D.T., Finberg, R.W., Kurt-Jones, E., Szabo, G. Gastroenterology (2004) [Pubmed]
  17. Recruitment of IkappaBalpha to the hes1 promoter is associated with transcriptional repression. Aguilera, C., Hoya-Arias, R., Haegeman, G., Espinosa, L., Bigas, A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  18. NF-kappaB RelA phosphorylation regulates RelA acetylation. Chen, L.F., Williams, S.A., Mu, Y., Nakano, H., Duerr, J.M., Buckbinder, L., Greene, W.C. Mol. Cell. Biol. (2005) [Pubmed]
  19. Regulation of constitutive p50/c-Rel activity via proteasome inhibitor-resistant IkappaBalpha degradation in B cells. O'Connor, S., Shumway, S.D., Amanna, I.J., Hayes, C.E., Miyamoto, S. Mol. Cell. Biol. (2004) [Pubmed]
  20. Identification of a novel NF-kappaB p50-related protein in B lymphocytes. Phillips, R.J., Gustafson, S., Ghosh, S. Mol. Cell. Biol. (1996) [Pubmed]
  21. Reductions in I kappa B epsilon and changes in NF-kappa B activity during B lymphocyte differentiation. Doerre, S., Mesires, K.P., Daley, K.M., McCarty, T., Knoetig, S., Corley, R.B. J. Immunol. (2005) [Pubmed]
  22. Aminosalicylic acid inhibits IkappaB kinase alpha phosphorylation of IkappaBalpha in mouse intestinal epithelial cells. Yan, F., Polk, D.B. J. Biol. Chem. (1999) [Pubmed]
  23. betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932. Lang, V., Janzen, J., Fischer, G.Z., Soneji, Y., Beinke, S., Salmeron, A., Allen, H., Hay, R.T., Ben-Neriah, Y., Ley, S.C. Mol. Cell. Biol. (2003) [Pubmed]
  24. IkappaB kinase-independent IkappaBalpha degradation pathway: functional NF-kappaB activity and implications for cancer therapy. Tergaonkar, V., Bottero, V., Ikawa, M., Li, Q., Verma, I.M. Mol. Cell. Biol. (2003) [Pubmed]
  25. Opposing roles for NF-kappa B/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1beta. Pizzi, M., Goffi, F., Boroni, F., Benarese, M., Perkins, S.E., Liou, H.C., Spano, P. J. Biol. Chem. (2002) [Pubmed]
  26. Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-kappa B. Asehnoune, K., Strassheim, D., Mitra, S., Kim, J.Y., Abraham, E. J. Immunol. (2004) [Pubmed]
  27. Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Deng, J., Lu, P.D., Zhang, Y., Scheuner, D., Kaufman, R.J., Sonenberg, N., Harding, H.P., Ron, D. Mol. Cell. Biol. (2004) [Pubmed]
  28. Developmental and tissue-specific expression of mouse pelle-like protein kinase. Trofimova, M., Sprenkle, A.B., Green, M., Sturgill, T.W., Goebl, M.G., Harrington, M.A. J. Biol. Chem. (1996) [Pubmed]
  29. Mechanisms underlying the protective potential of alpha-tocopherol (vitamin E) against haloperidol-associated neurotoxicity. Post, A., Rücker, M., Ohl, F., Uhr, M., Holsboer, F., Almeida, O.F., Michaelidis, T.M. Neuropsychopharmacology (2002) [Pubmed]
  30. In vivo and in vitro sensitization of leukemic cells to adriamycin-induced apoptosis by pentoxifylline. Involvement of caspase cascades and IkappaBalpha phosphorylation. Lerma-Díaz, J.M., Hernández-Flores, G., Domínguez-Rodríguez, J.R., Ortíz-Lazareno, P.C., Gómez-Contreras, P., Cervantes-Munguía, R., Scott-Algara, D., Aguilar-Lemarroy, A., Jave-Suárez, L.F., Bravo-Cuellar, A. Immunol. Lett. (2006) [Pubmed]
  31. Enhanced NF-kappaB activation and cellular function in macrophages lacking IkappaB kinase 1 (IKK1). Li, Q., Lu, Q., Bottero, V., Estepa, G., Morrison, L., Mercurio, F., Verma, I.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  32. Evidence that genetic deletion of the TNF receptor p60 or p80 in macrophages modulates RANKL-induced signaling. Takada, Y., Aggarwal, B.B. Blood (2004) [Pubmed]
  33. Lymphotoxin beta receptor induces sequential activation of distinct NF-kappa B factors via separate signaling pathways. Müller, J.R., Siebenlist, U. J. Biol. Chem. (2003) [Pubmed]
  34. Glycogen synthase kinase 3beta functions to specify gene-specific, NF-kappaB-dependent transcription. Steinbrecher, K.A., Wilson, W., Cogswell, P.C., Baldwin, A.S. Mol. Cell. Biol. (2005) [Pubmed]
  35. The IKK-2/Ikappa Balpha /NF-kappa B pathway plays a key role in the regulation of CCR3 and eotaxin-1 in fibroblasts. A critical link to dermatitis in Ikappa Balpha -deficient mice. Huber, M.A., Denk, A., Peter, R.U., Weber, L., Kraut, N., Wirth, T. J. Biol. Chem. (2002) [Pubmed]
  36. Vanadate induction of NF-kappaB involves IkappaB kinase beta and SAPK/ERK kinase 1 in macrophages. Chen, F., Demers, L.M., Vallyathan, V., Ding, M., Lu, Y., Castranova, V., Shi, X. J. Biol. Chem. (1999) [Pubmed]
  37. Haemorrhagic shock in mice - Intracellular signalling and immunomodulation of peritoneal macrophages' LPS response. Rani, M., Husain, B., Lendemans, S., Schade, F.U., Floh??, S. Immunobiology (2006) [Pubmed]
  38. Inhibition of nuclear factor kappaB and phosphatidylinositol 3-kinase/Akt is essential for massive hepatocyte apoptosis induced by tumor necrosis factor alpha in mice. Imose, M., Nagaki, M., Naiki, T., Osawa, Y., Brenner, D.A., Asano, T., Hayashi, H., Kato, T., Moriwaki, H. Liver Int. (2003) [Pubmed]
  39. Biphasic role of nuclear factor-kappa B on cell survival and COX-2 expression in SOD1 Tg astrocytes after oxygen glucose deprivation. Lee, Y.S., Song, Y.S., Giffard, R.G., Chan, P.H. J. Cereb. Blood Flow Metab. (2006) [Pubmed]
  40. I kappa B overexpression in cardiomyocytes prevents NF-kappa B translocation and provides cardioprotection in trauma. Carlson, D.L., White, D.J., Maass, D.L., Nguyen, R.C., Giroir, B., Horton, J.W. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
WikiGenes - Universities