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NFKBIA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases NFKBIA, IKBA, MAD-3, NFKBI, NFKB inhibitor alpha, EDAID2
External IDs OMIM: 164008 MGI: 104741 HomoloGene: 7863 GeneCards: NFKBIA
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_020529

NM_010907

RefSeq (protein)

NP_065390

NP_035037

Location (UCSC) Chr 14: 35.4 – 35.4 Mb Chr 12: 55.54 – 55.54 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; NFKBIA) is one member of a family of cellular proteins that function to inhibit the NF-κB transcription factor. IκBα inhibits NF-κB by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. [5] In addition, IκBα blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-κB's proper functioning. [6]

Disease linkage

The gene encoding the IκBα protein is mutated in some Hodgkin's lymphoma cells; such mutations inactivate the IκBα protein, thus causing NF-κB to be chronically active in the lymphoma tumor cells and this activity contributes to the malignant state of these tumor cells. [7]

Interactions

IκBα has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000100906Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021025Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Jacobs MD, Harrison SC (1998). "Structure of an IkappaBalpha/NF-kappaB complex". Cell. 95 (6): 749–58. doi: 10.1016/S0092-8674(00)81698-0. PMID  9865693. S2CID  7003353.
  6. ^ Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S (1995). "Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation". Genes Dev. 9 (22): 2723–35. doi: 10.1101/gad.9.22.2723. PMID  7590248.
  7. ^ Cabannes E, Khan G, Aillet F, Jarrett RF, Hay RT (1999). "Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha". Oncogene. 18 (20): 3063–70. doi: 10.1038/sj.onc.1202893. PMID  10340377. S2CID  8269256.
  8. ^ Suzuki H, Chiba T, Suzuki T, Fujita T, Ikenoue T, Omata M, Furuichi K, Shikama H, Tanaka K (January 2000). "Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination". J. Biol. Chem. 275 (4): 2877–84. doi: 10.1074/jbc.275.4.2877. PMID  10644755.
  9. ^ a b Spencer E, Jiang J, Chen ZJ (February 1999). "Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP". Genes Dev. 13 (3): 284–94. doi: 10.1101/gad.13.3.284. PMC  316434. PMID  9990853.
  10. ^ "Molecular Interaction Database". Archived from the original on 2006-05-06. Retrieved 2012-05-08.
  11. ^ a b c Cohen L, Henzel WJ, Baeuerle PA (September 1998). "IKAP is a scaffold protein of the IkappaB kinase complex". Nature. 395 (6699): 292–6. Bibcode: 1998Natur.395..292C. doi: 10.1038/26254. PMID  9751059. S2CID  4327300.
  12. ^ a b Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV (October 1997). "IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK". Science. 278 (5339): 866–9. Bibcode: 1997Sci...278..866W. doi: 10.1126/science.278.5339.866. PMID  9346485.
  13. ^ DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M (August 1997). "A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB". Nature. 388 (6642): 548–54. doi: 10.1038/41493. PMID  9252186. S2CID  4354442.
  14. ^ Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (March 1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature. 398 (6724): 252–6. Bibcode: 1999Natur.398..252N. doi: 10.1038/18465. PMID  10094049. S2CID  4421236.
  15. ^ Crépieux P, Kwon H, Leclerc N, Spencer W, Richard S, Lin R, Hiscott J (December 1997). "I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain". Mol. Cell. Biol. 17 (12): 7375–85. doi: 10.1128/MCB.17.12.7375. PMC  232593. PMID  9372968.
  16. ^ Prigent M, Barlat I, Langen H, Dargemont C (November 2000). "IkappaBalpha and IkappaBalpha /NF-kappa B complexes are retained in the cytoplasm through interaction with a novel partner, RasGAP SH3-binding protein 2". J. Biol. Chem. 275 (46): 36441–9. doi: 10.1074/jbc.M004751200. PMID  10969074.
  17. ^ a b c Hay DC, Kemp GD, Dargemont C, Hay RT (May 2001). "Interaction between hnRNPA1 and IkappaBalpha is required for maximal activation of NF-kappaB-dependent transcription". Mol. Cell. Biol. 21 (10): 3482–90. doi: 10.1128/MCB.21.10.3482-3490.2001. PMC  100270. PMID  11313474.
  18. ^ Mercurio F, Murray BW, Shevchenko A, Bennett BL, Young DB, Li JW, Pascual G, Motiwala A, Zhu H, Mann M, Manning AM (February 1999). "IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex". Mol. Cell. Biol. 19 (2): 1526–38. doi: 10.1128/mcb.19.2.1526. PMC  116081. PMID  9891086.
  19. ^ a b Malek S, Huxford T, Ghosh G (September 1998). "Ikappa Balpha functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-kappaB". J. Biol. Chem. 273 (39): 25427–35. doi: 10.1074/jbc.273.39.25427. PMID  9738011.
  20. ^ Chang NS (March 2002). "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. 277 (12): 10323–31. doi: 10.1074/jbc.M106607200. PMID  11799106.
  21. ^ Fischle W, Verdin E, Greene WC (August 2001). "Duration of nuclear NF-kappaB action regulated by reversible acetylation". Science. 293 (5535): 1653–7. Bibcode: 2001Sci...293.1653C. doi: 10.1126/science.1062374. hdl: 11858/00-001M-0000-002C-9FF1-A. PMID  11533489. S2CID  45796404.
  22. ^ Kiernan R, Brès V, Ng RW, Coudart MP, El Messaoudi S, Sardet C, Jin DY, Emiliani S, Benkirane M (January 2003). "Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65". J. Biol. Chem. 278 (4): 2758–66. doi: 10.1074/jbc.M209572200. PMID  12419806.
  23. ^ Hansen SK, Baeuerle PA, Blasi F (April 1994). "Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription". Mol. Cell. Biol. 14 (4): 2593–603. doi: 10.1128/mcb.14.4.2593. PMC  358627. PMID  8139561.
  24. ^ Schouten GJ, Vertegaal AC, Whiteside ST, Israël A, Toebes M, Dorsman JC, van der Eb AJ, Zantema A (June 1997). "IkappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase". EMBO J. 16 (11): 3133–44. doi: 10.1093/emboj/16.11.3133. PMC  1169932. PMID  9214631.
  25. ^ Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D, Zheng W, Purohit S, Podolsky RH, Muir A, Wang J, Dong Z, Brusko T, Atkinson M, Pozzilli P, Zeidler A, Raffel LJ, Jacob CO, Park Y, Serrano-Rios M, Larrad MT, Zhang Z, Garchon HJ, Bach JF, Rotter JI, She JX, Wang CY (August 2004). "A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes". Nat. Genet. 36 (8): 837–41. doi: 10.1038/ng1391. PMID  15247916. S2CID  41123857.
  26. ^ Dai RM, Chen E, Longo DL, Gorbea CM, Li CC (February 1998). "Involvement of valosin-containing protein, an ATPase Co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha". J. Biol. Chem. 273 (6): 3562–73. doi: 10.1074/jbc.273.6.3562. PMID  9452483.

Further reading

External links