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I?Ba (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-?B transcription factor. I?Ba inhibits NF-?B by masking the nuclear localization signals (NLS) of NF-?B proteins and keeping them sequestered in an inactive state in the cytoplasm.[1] In addition, I?Ba blocks the ability of NF-?B transcription factors to bind to DNA, which is required for NF-?B's proper functioning.[2]
Disease linkage
The gene encoding the I?Ba protein is mutated in some Hodgkin's lymphoma cells; such mutations inactivate the I?Ba protein, thus causing NF-?B to be chronically active in the lymphoma tumor cells and this activity contributes to the malignant state of these tumor cells.[3]
References
- ^ 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.
- ^ 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.
- ^ 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.
Further reading
- Roulston A, Lin R, Beauparlant P, et al. (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. 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. PMID 10582246.
- Muthumani K, Desai BM, Hwang DS, et al. (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, et al. (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: 11. doi:10.1186/1742-4690-2-11. 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.
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