IκBα

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Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
1NFI.png
Crystallographic structure (PDB 1NFI) of I?B? (magenta) complexed with a homodimer of the NF-?B heterodimeric protein (p65 - cyan and p50 - green).
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NFKBIA ; IKBA; MAD-3; NFKBI
External IDs OMIM164008 MGI104741 HomoloGene7863 ChEMBL: 2898 GeneCards: NFKBIA Gene
RNA expression pattern
PBB GE NFKBIA 201502 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4792 18035
Ensembl ENSG00000100906 ENSMUSG00000021025
UniProt P25963 Q9Z1E3
RefSeq (mRNA) NM_020529 NM_010907
RefSeq (protein) NP_065390 NP_035037
Location (UCSC) Chr 14:
35.87 – 35.87 Mb
Chr 12:
55.49 – 55.49 Mb
PubMed search [1] [2]

IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) 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.[1] In addition, IκBα blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-κB's proper functioning.[2]

Disease linkage[edit]

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.[3]

Interactions[edit]

IκBα has been shown to interact with:

References[edit]

  1. ^ Jacobs M, Harrison S (1998). "Structure of an IkappaBalpha/NF-kappaB complex". Cell 95 (6): 749–58. doi:10.1016/S0092-8674(00)81698-0. PMID 9865693. 
  2. ^ Verma I, Stevenson J, Schwarz E, 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. 
  3. ^ Cabannes E, Khan G, Aillet F, Jarrett R, Hay R (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. 
  4. ^ Suzuki H, Chiba T, Suzuki T, Fujita T, Ikenoue T, Omata M et al. (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. PMID 10644755. 
  5. ^ a b Spencer E, Jiang J, Chen Z (February 1999). "Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP". Genes Dev. 13 (3): 284–94. PMC 316434. PMID 9990853. 
  6. ^ "Molecular Interaction Database". 
  7. ^ a b c Cohen L, Henzel W, Baeuerle P (September 1998). "IKAP is a scaffold protein of the IkappaB kinase complex". Nature 395 (6699): 292–6. doi:10.1038/26254. PMID 9751059. 
  8. ^ a b Woronicz J, Gao X, Cao Z, Rothe M, Goeddel D (October 1997). "IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK". Science 278 (5339): 866–9. PMID 9346485. 
  9. ^ DiDonato J, Hayakawa M, Rothwarf D, 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. 
  10. ^ 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. doi:10.1038/18465. PMID 10094049. 
  11. ^ Crépieux P, Kwon H, Leclerc N, Spencer W, Richard S, Lin R et al. (December 1997). "I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain". Mol. Cell. Biol. 17 (12): 7375–85. PMC 232593. PMID 9372968. 
  12. ^ 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. 
  13. ^ a b c Hay D, Kemp G, Dargemont C, Hay R (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. 
  14. ^ Mercurio F, Murray B, Shevchenko A, Bennett B, Young D, Li J et al. (February 1999). "IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex". Mol. Cell. Biol. 19 (2): 1526–38. PMC 116081. PMID 9891086. 
  15. ^ 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. PMID 9738011. 
  16. ^ Chang N (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. 
  17. ^ Fischle W, Verdin E, Greene W (August 2001). "Duration of nuclear NF-kappaB action regulated by reversible acetylation". Science 293 (5535): 1653–7. doi:10.1126/science.1062374. PMID 11533489. 
  18. ^ Kiernan R, Brès V, Ng R, Coudart M, El Messaoudi S, Sardet C et al. (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. 
  19. ^ Hansen S, Baeuerle P, 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. PMC 358627. PMID 8139561. 
  20. ^ Schouten G, Vertegaal A, Whiteside S, Israël A, Toebes M, Dorsman J et al. (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. 
  21. ^ Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D et al. (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. 
  22. ^ Dai R, Chen E, Longo D, Gorbea C, Li C (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. PMID 9452483. 

Further reading[edit]

External links[edit]