IκBα

From Wikipedia, the free encyclopedia

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

Crystallographic structure (PDB 1NHI) of IκBα (magenta) complexed with a homodimer of the NF-κB heterodimeric protein (p65 - cyan and p50 - green).

Available structures: 1ikn, 1nfi

Identifiers

Symbol(s)

NFKBIA; IKBA; MAD-3; NFKBI

External IDs

OMIM: 164008 MGI: 104741 HomoloGene: 7863

Gene ontology
Molecular Function:	• nuclear localization sequence binding • ubiquitin protein ligase binding • NF-kappaB binding
Cellular Component:	• nucleus • cytoplasm • cytosol
Biological Process:	• protein import into nucleus, translocation • apoptosis • cytoplasmic sequestering of NF-kappaB • regulation of cell proliferation • regulation of NF-kappaB import into nucleus • negative regulation of DNA binding • negative regulation of myeloid cell differentiation • negative regulation of Notch signaling pathway

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_020529 (mRNA)
NP_065390 (protein)

NM_010907 (mRNA)
NP_035037 (protein)

Location

Chr 14: 34.94 - 34.94 Mb

Chr 12: 56.41 - 56.41 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]

1 Disease linkage
2 References
3 Further reading
4 External links

[edit] 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.^[3]

[edit] 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.

[edit] 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.