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]
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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]
IκBα has been shown to interact with:
- BTRC,[8][9]
- C22orf25,[10]
- CHUK,[11][12][13][14]
- DYNLL1,[15]
- G3BP2,[16]
- Heterogeneous nuclear ribonucleoprotein A1,[17]
- IKK2,[11][12][18]
- NFKB1,[17][19]
- P53,[20]
- RELA,[9][11][17][19][21][22][23]
- RPS6KA1,[24]
- SUMO4,[25] and
- Valosin-containing protein.[26]
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. 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.
- Roulston A, Lin R, Beauparlant P, Wainberg MA, Hiscott J (1995). "Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B/Rel transcription factors". Microbiol. Rev. 59 (3): 481–505. doi:10.1128/MMBR.59.3.481-505.1995. PMC 239370. PMID 7565415.
- Hay RT, Vuillard L, Desterro JM, Rodriguez MS (2000). "Control of NF-kappa B transcriptional activation by signal induced proteolysis of I kappa B alpha". Philos. Trans. R. Soc. Lond. B Biol. Sci. 354 (1389): 1601–9. doi:10.1098/rstb.1999.0504. PMC 1692667. PMID 10582246.
- Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB (2004). "HIV-1 Vpr and anti-inflammatory activity". DNA Cell Biol. 23 (4): 239–47. doi:10.1089/104454904773819824. PMID 15142381.
- Caraglia M, Marra M, Pelaia G, Maselli R, Caputi M, Marsico SA, Abbruzzese A (2005). "Alpha-interferon and its effects on signal transduction pathways". J. Cell. Physiol. 202 (2): 323–35. doi:10.1002/jcp.20137. PMID 15389589.
- Le Rouzic E, Benichou S (2006). "The Vpr protein from HIV-1: distinct roles along the viral life cycle". Retrovirology. 2 (1): 11. doi:10.1186/1742-4690-2-11. PMC 554975. PMID 15725353.
- Zhao RY, Bukrinsky M, Elder RT (2005). "HIV-1 viral protein R (Vpr) & host cellular responses". Indian J. Med. Res. 121 (4): 270–86. PMID 15817944.
- Sun XF, Zhang H (2007). "NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases". Histol. Histopathol. 22 (12): 1387–98. PMID 17701919.
