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

NFKBIB  -  nuclear factor of kappa light polypeptide...

Homo sapiens

Synonyms: I-kappa-B-beta, IKBB, IkB-B, IkB-beta, IkappaBbeta, ...
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 NFKBIB

  • Despite the dual specificity of HTLV-1 Tax for IkappaBalpha and IkappaBbeta at the protein level, Tax selectively stimulates NF-kappaB-directed transcription of the IkappaBalpha gene [1].
  • To understand the mechanisms of constitutive NF-kappaB activation, we have analyzed the function of IkappaBalpha and IkappaBbeta in breast cancer cells [2].
  • Inhibition of IFN-beta expression directly correlated with a reduction in the binding of NF-kappaB (p50-RelA) complex to PRDII after Sendai virus infection in IkappaBalpha-expressing cells, whereas IFN-beta expression and NF-kappaB binding were only slightly reduced in IkappaBbeta-expressing cells [3].
  • Persistent HIV infection of these cells results in increased levels of NF-kappaB in the nucleus secondary to increased IkappaBalpha, IkappaBbeta, and IkappaBepsilon degradation, a mechanism postulated to regulate viral persistence [4].
  • Immunoblot analysis of IkappaBbeta from mouse colonocytes and the human HT-29 colon cancer cell line indicated that most of the IkappaBbeta in these cells was similar to the C-terminal-truncated IkappaBbeta2 isoform [5].

High impact information on NFKBIB

  • Swapping a putative beta-turn within the first ankyrin repeat between the strong Ikappa Balpha and the weak IkappaBbeta inhibitors switches their in vivo inhibitory activity on NF-kappaB [6].
  • Removal of cellular kappaB-Ras enhances whereas excess kappaB-Ras blocks induced IkappaBbeta degradation [7].
  • We show that although IkappaBalpha and another IkappaB member, IkappaBbeta, can enter the nucleus and repress NF-kappaB DNA-binding activity during the postinduction phase, only IkappaBalpha allows the efficient export of nuclear NF-kappaB [8].
  • However, the level of IkappaBbeta was unchanged for HL-60 cells undergoing PDT-induced apoptosis [9].
  • CD28 mediates a potent costimulatory signal for rapid degradation of IkappaBbeta which is associated with accelerated activation of various NF-kappaB/Rel heterodimers [10].

Biological context of NFKBIB


Anatomical context of NFKBIB


Associations of NFKBIB with chemical compounds

  • Similarly, a complex between NF-kappaB and a mutant IkappaBbeta protein containing four serine to alanine mutations within its C-terminal proline, glutamic acid, serine, and threonine-rich sequence exhibits nucleocytoplasmic shuttling [12].
  • Third, mutants of IkappaBbeta that are defective for phosphorylation at Ser-313 and Ser-315 fail to efficiently block NF-kappaB-directed transcription in vivo, whereas replacement of these two IkappaBbeta residues with a phosphoserine mimetic generates a fully functional repressor [17].
  • RXR is a nuclear protein, whereas IkappaBbeta accumulates in the nucleus only in cells stimulated with lipopolysaccharide or other inducers that result in prolonged activation of NFkappaB [18].
  • Consistent with this, cotransfection with IkappaBbeta specifically repressed the 9-cis-RA-induced transcriptional activities of RXR in an lipopolysaccharide-dependent manner [18].
  • In contrast to uninfected cells, the addition of recombinant glutathione S-transferase-IkappaBalpha protein to preformed NF-kappaB.DNA complexes from HIV-1-infected cell extracts did not completely dissociate the complexes, suggesting that IkappaBbeta may protect NF-kappaB complexes from IkappaBalpha-mediated dissociation [16].

Physical interactions of NFKBIB


Enzymatic interactions of NFKBIB

  • In conclusion, in the ERK signaling cascade, RSK1 is a key component that directly phosphorylates IkappaBbeta and contributes to the persistent activation of NF-kappaB by IL-1beta [20].

Regulatory relationships of NFKBIB

  • We demonstrate that NaSal similarly inhibits TNF-induced IkappaBbeta degradation in a p38-dependent manner [21].

Other interactions of NFKBIB

  • In these cells, NFkappaB retains DNA binding activity for up to 72 h despite the presence of resynthesized IkappaBalpha and in the absence of IkappaBbeta [22].
  • beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta [19].
  • A small Ras-like G-protein, kappaB-Ras, participates with the IkappaBbeta insert to effectively mask the NF-kappaB nuclear localization potential [12].
  • We noted that extracts containing Tax had extremely low levels of IkappaBbeta, but not IkappaBalpha, and contained predominantly a truncated form of the MAP3K MEKK1 [23].
  • Although the two IkappaB proteins are significantly homologous, IkappaBbeta contains a unique 47-amino acid insertion of unknown function within its ankyrin repeat domain [12].

Analytical, diagnostic and therapeutic context of NFKBIB


  1. Inactivation of IkappaBbeta by the tax protein of human T-cell leukemia virus type 1: a potential mechanism for constitutive induction of NF-kappaB. McKinsey, T.A., Brockman, J.A., Scherer, D.C., Al-Murrani, S.W., Green, P.L., Ballard, D.W. Mol. Cell. Biol. (1996) [Pubmed]
  2. Negative regulation of transactivation function but not DNA binding of NF-kappaB and AP-1 by IkappaBbeta1 in breast cancer cells. Newton, T.R., Patel, N.M., Bhat-Nakshatri, P., Stauss, C.R., Goulet, R.J., Nakshatri, H. J. Biol. Chem. (1999) [Pubmed]
  3. IkappaB-mediated inhibition of virus-induced beta interferon transcription. Algarté, M., Nguyen, H., Heylbroeck, C., Lin, R., Hiscott, J. J. Virol. (1999) [Pubmed]
  4. 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]
  5. IkappaBbeta-related proteins in normal and transformed colonic epithelial cells. Inan, M.S., Place, R., Tolmacheva, V., Wang, Q.S., Hubbard, A.K., Rosenberg, D.W., Giardina, C. Mol. Carcinog. (2000) [Pubmed]
  6. Mechanisms by which IkappaB proteins control NF-kappaB activity. Simeonidis, S., Stauber, D., Chen, G., Hendrickson, W.A., Thanos, D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Inhibition of NF-kappaB activity by IkappaBbeta in association with kappaB-Ras. Chen, Y., Vallee, S., Wu, J., Vu, D., Sondek, J., Ghosh, G. Mol. Cell. Biol. (2004) [Pubmed]
  8. Postrepression activation of NF-kappaB requires the amino-terminal nuclear export signal specific to IkappaBalpha. Huang, T.T., Miyamoto, S. Mol. Cell. Biol. (2001) [Pubmed]
  9. Nuclear factor-kappaB activation by the photochemotherapeutic agent verteporfin. Granville, D.J., Carthy, C.M., Jiang, H., Levy, J.G., McManus, B.M., Matroule, J.Y., Piette, J., Hunt, D.W. Blood (2000) [Pubmed]
  10. CD28 mediates a potent costimulatory signal for rapid degradation of IkappaBbeta which is associated with accelerated activation of various NF-kappaB/Rel heterodimers. Harhaj, E.W., Maggirwar, S.B., Good, L., Sun, S.C. Mol. Cell. Biol. (1996) [Pubmed]
  11. Assignment of the IkappaB-beta gene NFKBIB to human chromosome band 19q13.1 by in situ hybridization. Okamoto, T., Ono, T., Hori, M., Yang, J.P., Tetsuka, T., Kawabe, T., Sonta, S. Cytogenet. Cell Genet. (1998) [Pubmed]
  12. KappaB-Ras binds to the unique insert within the ankyrin repeat domain of IkappaBbeta and regulates cytoplasmic retention of IkappaBbeta x NF-kappaB complexes. Chen, Y., Wu, J., Ghosh, G. J. Biol. Chem. (2003) [Pubmed]
  13. Regulation of IkappaBbeta expression in testis. Budde, L.M., Wu, C., Tilman, C., Douglas, I., Ghosh, S. Mol. Biol. Cell (2002) [Pubmed]
  14. Expression of nuclear factor kappa B components in human endometrium. Page, M., Tuckerman, E.M., Li, T.C., Laird, S.M. J. Reprod. Immunol. (2002) [Pubmed]
  15. Involvement of NF-kappaB and c-myc signaling pathways in the apoptosis of HL-60 cells induced by alkaloids of Tripterygium hypoglaucum (levl.) Hutch. Zhuang, W.J., Fong, C.C., Cao, J., Ao, L., Leung, C.H., Cheung, H.Y., Xiao, P.G., Fong, W.F., Yang, M.S. Phytomedicine (2004) [Pubmed]
  16. Nuclear IkappaBbeta maintains persistent NF-kappaB activation in HIV-1-infected myeloid cells. DeLuca, C., Petropoulos, L., Zmeureanu, D., Hiscott, J. J. Biol. Chem. (1999) [Pubmed]
  17. Phosphorylation of the PEST domain of IkappaBbeta regulates the function of NF-kappaB/IkappaBbeta complexes. McKinsey, T.A., Chu, Z.L., Ballard, D.W. J. Biol. Chem. (1997) [Pubmed]
  18. IkappaBbeta interacts with the retinoid X receptor and inhibits retinoid-dependent transactivation in lipopolysaccharide-treated cells. Na, S.Y., Kim, H.J., Lee, S.K., Choi, H.S., Na, D.S., Lee, M.O., Chung, M., Moore, D.D., Lee, J.W. J. Biol. Chem. (1998) [Pubmed]
  19. beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta. Wu, C., Ghosh, S. J. Biol. Chem. (1999) [Pubmed]
  20. Ribosomal S6 kinase-1 modulates interleukin-1beta-induced persistent activation of NF-{kappa}B through phosphorylation of I{kappa}Bbeta. Xu, S., Bayat, H., Hou, X., Jiang, B. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  21. Cell stress and MKK6b-mediated p38 MAP kinase activation inhibit tumor necrosis factor-induced IkappaB phosphorylation and NF-kappaB activation. Alpert, D., Schwenger, P., Han, J., Vilcek, J. J. Biol. Chem. (1999) [Pubmed]
  22. 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]
  23. The human T-cell leukemia virus type-1 Tax protein regulates the activity of the IkappaB kinase complex. Li, X.H., Murphy, K.M., Palka, K.T., Surabhi, R.M., Gaynor, R.B. J. Biol. Chem. (1999) [Pubmed]
  24. 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]
  25. Lipopolysaccharide-induced NF-kappaB activation in human endothelial cells involves degradation of IkappaBalpha but not IkappaBbeta. Zen, K., Karsan, A., Eunson, T., Yee, E., Harlan, J.M. Exp. Cell Res. (1998) [Pubmed]
  26. Interleukin-8 up-regulation by neutrophil elastase is mediated by MyD88/IRAK/TRAF-6 in human bronchial epithelium. Walsh, D.E., Greene, C.M., Carroll, T.P., Taggart, C.C., Gallagher, P.M., O'Neill, S.J., McElvaney, N.G. J. Biol. Chem. (2001) [Pubmed]
WikiGenes - Universities