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Gene Review

NFKBIA  -  nuclear factor of kappa light polypeptide...

Homo sapiens

Synonyms: I-kappa-B-alpha, IKBA, IkB-alpha, IkappaBalpha, MAD-3, ...
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Disease relevance of NFKBIA


Psychiatry related information on NFKBIA


High impact information on NFKBIA

  • The position of the sixth ankyrin repeat shows that full-length IkappaBalpha will occlude the NF-kappaB DNA-binding cleft [8].
  • It shows a stack of six IkappaBalpha ankyrin repeats facing the C-terminal domains of the NF-kappaB Rel homology regions [8].
  • Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity [9].
  • The MAD-3 cDNA encodes an I kappa B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa B, including adhesion-dependent pathways of monocyte activation [10].
  • Surprisingly, GR was recruited to both of these elements, despite the fact that GR failed to repress the IkappaBalpha promoter [11].

Chemical compound and disease context of NFKBIA


Biological context of NFKBIA


Anatomical context of NFKBIA


Associations of NFKBIA with chemical compounds


Physical interactions of NFKBIA


Enzymatic interactions of NFKBIA


Regulatory relationships of NFKBIA

  • beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha [31].
  • We also show that a S32/36 IkappaBalpha mutant blocks EGFR-induced NF-kappaB activation [39].
  • In addition, overexpression of the dominant inhibitory mutant (S32A/S36A) of IkappaBalpha inhibited PMA-stimulated and RSK1-enhanced megakaryocytic differentiation, indicating that NF-kappaB mediates a signal for megakaryocytic differentiation downstream of RSK1 [40].
  • In addition, treatment with SFN and PEITC potently inhibited phosphorylation of both IKKbeta and IKKalpha and significantly inhibited the in vitro phosphorylation of IkappaBalpha mediated by IKKbeta [4].
  • Analogous to treatments with SFN and PEITC, SR-IkappaBalpha also strongly inhibited NF-kappaB transcriptional activity as well as VEGF, cylcin D1, and Bcl-X(L) expression [4].

Other interactions of NFKBIA

  • Thus, SUMO-1-modified IkappaBalpha cannot be ubiquitinated and is resistant to proteasome-mediated degradation [19].
  • By using a yeast two-hybrid screen, we identified the inhibitor of NF-kappaB, IkappaBalpha, as a binding partner of beta-arrestin 1 [31].
  • This transcription factor is regulated by a family of structurally related inhibitors including IkappaBalpha, IkappaBbeta, and IkappaBepsilon, which trap NF-kappaB in the cytoplasm [41].
  • In the resting cell, RhoA suppresses Cdc42 activation, IkappaBalpha degradation, nuclear factor-kappaB (NF-kappaB) activation, and induction of TNFalpha and NF-kappaB-dependent chemokines [42].
  • Suppression of NF-kappaB activity in PC-3 cells by a mutant IkappaBalpha super-repressor adenoviral vector decreased the CXCR4 mRNA expression and inhibited adhesion and TEM [43].

Analytical, diagnostic and therapeutic context of NFKBIA


  1. Radiosensitization by inhibition of IkappaB-alpha phosphorylation in human glioma cells. Ding, G.R., Honda, N., Nakahara, T., Tian, F., Yoshida, M., Hirose, H., Miyakoshi, J. Radiat. Res. (2003) [Pubmed]
  2. Polymorphic variants of NFKB1 and its inhibitory protein NFKBIA, and their involvement in sporadic breast cancer. Curran, J.E., Weinstein, S.R., Griffiths, L.R. Cancer Lett. (2002) [Pubmed]
  3. A polymorphism of the NFKBIA gene is associated with Crohn's disease patients lacking a predisposing allele of the CARD15 gene. Klein, W., Tromm, A., Folwaczny, C., Hagedorn, M., Duerig, N., Epplen, J.T., Schmiegel, W.H., Griga, T. International journal of colorectal disease. (2004) [Pubmed]
  4. Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Xu, C., Shen, G., Chen, C., Gélinas, C., Kong, A.N. Oncogene (2005) [Pubmed]
  5. The synthetic epoxyquinoids jesterone dimer and epoxyquinone A monomer induce apoptosis and inhibit REL (human c-Rel) DNA binding in an IkappaBalpha-deficient diffuse large B-cell lymphoma cell line. Liang, M.C., Bardhan, S., Porco, J.A., Gilmore, T.D. Cancer Lett. (2006) [Pubmed]
  6. Adenosine signaling mediates SUMO-1 modification of IkappaBalpha during hypoxia and reoxygenation. Liu, Q., Li, J., Khoury, J., Colgan, S.P., Ibla, J.C. J. Biol. Chem. (2009) [Pubmed]
  7. Moderate alcohol intake in humans attenuates monocyte inflammatory responses: inhibition of nuclear regulatory factor kappa B and induction of interleukin 10. Mandrekar, P., Catalano, D., White, B., Szabo, G. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  8. Structure of an IkappaBalpha/NF-kappaB complex. Jacobs, M.D., Harrison, S.C. Cell (1998) [Pubmed]
  9. Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. Chen, Z.J., Parent, L., Maniatis, T. Cell (1996) [Pubmed]
  10. Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. Haskill, S., Beg, A.A., Tompkins, S.M., Morris, J.S., Yurochko, A.D., Sampson-Johannes, A., Mondal, K., Ralph, P., Baldwin, A.S. Cell (1991) [Pubmed]
  11. The glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression. Luecke, H.F., Yamamoto, K.R. Genes Dev. (2005) [Pubmed]
  12. Tyrosine kinase p56lck regulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through tyrosine phosphorylation of IkappaBalpha following hypoxia/reoxygenation. Mahabeleshwar, G.H., Kundu, G.C. J. Biol. Chem. (2003) [Pubmed]
  13. Tumor necrosis factor-alpha-induced apoptosis in prostate cancer cells through inhibition of nuclear factor-kappaB by an IkappaBalpha "super-repressor". Muenchen, H.J., Lin, D.L., Walsh, M.A., Keller, E.T., Pienta, K.J. Clin. Cancer Res. (2000) [Pubmed]
  14. Ikappakappa mediates NF-kappaB activation in human immunodeficiency virus-infected cells. Asin, S., Taylor, J.A., Trushin, S., Bren, G., Paya, C.V. J. Virol. (1999) [Pubmed]
  15. Nuclear factor kappaB activation by muscarinic receptors in astroglial cells: effect of ethanol. Guizzetti, M., Bordi, F., Dieguez-Acuña, F.J., Vitalone, A., Madia, F., Woods, J.S., Costa, L.G. Neuroscience (2003) [Pubmed]
  16. Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells. Faith, S.A., Sweet, T.J., Bailey, E., Booth, T., Docherty, J.J. Antiviral Res. (2006) [Pubmed]
  17. Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Miterski, B., Böhringer, S., Klein, W., Sindern, E., Haupts, M., Schimrigk, S., Epplen, J.T. Genes Immun. (2002) [Pubmed]
  18. Association of nuclear factor-kappaB in psoriatic arthritis. Butt, C., Sun, S., Peddle, L., Greenwood, C., Hamilton, S., Gladman, D., Rahman, P. J. Rheumatol. (2005) [Pubmed]
  19. SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation. Desterro, J.M., Rodriguez, M.S., Hay, R.T. Mol. Cell (1998) [Pubmed]
  20. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Rosenstiel, P., Fantini, M., Bräutigam, K., Kühbacher, T., Waetzig, G.H., Seegert, D., Schreiber, S. Gastroenterology (2003) [Pubmed]
  21. Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF-kappa B: positive regulation by members of the rel/NF-kappa B family. Le Bail, O., Schmidt-Ullrich, R., Israël, A. EMBO J. (1993) [Pubmed]
  22. NF-kappa B regulation in human neutrophils by nuclear I kappa B alpha: correlation to apoptosis. Castro-Alcaraz, S., Miskolci, V., Kalasapudi, B., Davidson, D., Vancurova, I. J. Immunol. (2002) [Pubmed]
  23. Persistent interleukin-1beta signaling causes long term activation of NFkappaB in a promoter-specific manner in human glial cells. Griffin, B.D., Moynagh, P.N. J. Biol. Chem. (2006) [Pubmed]
  24. Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Liu, J., Suresh Kumar, K.G., Yu, D., Molton, S.A., McMahon, M., Herlyn, M., Thomas-Tikhonenko, A., Fuchs, S.Y. Oncogene (2007) [Pubmed]
  25. Inhibition of the NF-kappaB pathway by varicella-zoster virus in vitro and in human epidermal cells in vivo. Jones, J.O., Arvin, A.M. J. Virol. (2006) [Pubmed]
  26. PI-3K/Akt and NF-kappaB/IkappaBalpha pathways are activated in Jurkat T cells in response to TRAIL treatment. Zauli, G., Sancilio, S., Cataldi, A., Sabatini, N., Bosco, D., Di Pietro, R. J. Cell. Physiol. (2005) [Pubmed]
  27. A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes. Huang, T.T., Kudo, N., Yoshida, M., Miyamoto, S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  28. Hodgkin disease: pharmacologic intervention of the CD40-NF kappa B pathway by a protease inhibitor. Annunziata, C.M., Safiran, Y.J., Irving, S.G., Kasid, U.N., Cossman, J. Blood (2000) [Pubmed]
  29. Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase. Takada, Y., Mukhopadhyay, A., Kundu, G.C., Mahabeleshwar, G.H., Singh, S., Aggarwal, B.B. J. Biol. Chem. (2003) [Pubmed]
  30. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents. Sandur, S.K., Ichikawa, H., Sethi, G., Ahn, K.S., Aggarwal, B.B. J. Biol. Chem. (2006) [Pubmed]
  31. beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Witherow, D.S., Garrison, T.R., Miller, W.E., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  32. I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding. Ganchi, P.A., Sun, S.C., Greene, W.C., Ballard, D.W. Mol. Biol. Cell (1992) [Pubmed]
  33. IkappaBalpha-dependent regulation of low-shear flow-induced NF-kappa B activity: role of nitric oxide. Mohan, S., Hamuro, M., Sorescu, G.P., Koyoma, K., Sprague, E.A., Jo, H., Valente, A.J., Prihoda, T.J., Natarajan, M. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  34. Kinetic mechanisms of IkappaB-related kinases (IKK) inducible IKK and TBK-1 differ from IKK-1/IKK-2 heterodimer. Huynh, Q.K., Kishore, N., Mathialagan, S., Donnelly, A.M., Tripp, C.S. J. Biol. Chem. (2002) [Pubmed]
  35. IkappaBalpha (inhibitory kappaBalpha) identified as labile repressor of MnSOD (manganese superoxide dismutase) expression. Kiningham, K.K., Daosukho, C., St Clair, D.K. Biochem. J. (2004) [Pubmed]
  36. beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta. Wu, C., Ghosh, S. J. Biol. Chem. (1999) [Pubmed]
  37. Chemokine IL-8 induction by particulate wear debris in osteoblasts is mediated by NF-kappaB. Fritz, E.A., Jacobs, J.J., Glant, T.T., Roebuck, K.A. J. Orthop. Res. (2005) [Pubmed]
  38. Identification of IkappaBalpha as a substrate of Fas-associated phosphatase-1. Nakai, Y., Irie, S., Sato, T.A. Eur. J. Biochem. (2000) [Pubmed]
  39. The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome. Habib, A.A., Chatterjee, S., Park, S.K., Ratan, R.R., Lefebvre, S., Vartanian, T. J. Biol. Chem. (2001) [Pubmed]
  40. Extracellular signal-regulated kinase/90-KDA ribosomal S6 kinase/nuclear factor-kappa B pathway mediates phorbol 12-myristate 13-acetate-induced megakaryocytic differentiation of K562 cells. Kim, K.W., Kim, S.H., Lee, E.Y., Kim, N.D., Kang, H.S., Kim, H.D., Chung, B.S., Kang, C.D. J. Biol. Chem. (2001) [Pubmed]
  41. IkappaB kinase complex is an intracellular target for endotoxic lipopolysaccharide in human monocytic cells. Hawiger, J., Veach, R.A., Liu, X.Y., Timmons, S., Ballard, D.W. Blood (1999) [Pubmed]
  42. Dual role for RhoA in suppression and induction of cytokines in the human neutrophil. Fessler, M.B., Arndt, P.G., Just, I., Nick, J.A., Malcolm, K.C., Scott Worthen, G. Blood (2007) [Pubmed]
  43. Up-regulation of CXCR4 expression in PC-3 cells by stromal-derived factor-1alpha (CXCL12) increases endothelial adhesion and transendothelial migration: role of MEK/ERK signaling pathway-dependent NF-kappaB activation. Kukreja, P., Abdel-Mageed, A.B., Mondal, D., Liu, K., Agrawal, K.C. Cancer Res. (2005) [Pubmed]
  44. Cytoplasmic IkappaBalpha increases NF-kappaB-independent transcription through binding to histone deacetylase (HDAC) 1 and HDAC3. Viatour, P., Legrand-Poels, S., van Lint, C., Warnier, M., Merville, M.P., Gielen, J., Piette, J., Bours, V., Chariot, A. J. Biol. Chem. (2003) [Pubmed]
  45. Angiotensin II induces the expression of tissue factor and its mechanism in human monocytes. He, M., He, X., Xie, Q., Chen, F., He, S. Thromb. Res. (2006) [Pubmed]
  46. Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer. Zerbini, L.F., Wang, Y., Cho, J.Y., Libermann, T.A. Cancer Res. (2003) [Pubmed]
  47. Constitutive activation of NF-kappaB in Ki-ras-transformed prostate epithelial cells. Kim, B.Y., Gaynor, R.B., Song, K., Dritschilo, A., Jung, M. Oncogene (2002) [Pubmed]
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