関: I-kappa B

WordNet

the 2nd letter of the Roman alphabet (同)b
the blood group whose red cells carry the B antigen (同)type_B, group B
any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
the 9th letter of the Roman alphabet (同)i
the 10th letter of the Greek alphabet

PrepTutorEJDIC

蛋白(たんばく)質
『私は』私が
iodineの化学記号
カッパ(ギリシア語アルファベットの第10字Κ,k;英語の『K,k』に相当)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/27 17:14:54」(JST)

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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

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

IκBα has been shown to interact with:

BTRC,^[4]^[5]
C22orf25,^[6]
CHUK,^[7]^[8]^[9]^[10]
DYNLL1,^[11]
G3BP2,^[12]
Heterogeneous nuclear ribonucleoprotein A1,^[13]
IKK2,^[7]^[8]^[14]
NFKB1,^[13]^[15]
P53,^[16]
RELA,^[5]^[7]^[13]^[15]^[17]^[18]^[19]
RPS6KA1,^[20]
SUMO4,^[21] and
Valosin-containing protein.^[22]

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.
^ 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.
^ ^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.
^ "Molecular Interaction Database".
^ ^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. doi:10.1038/26254. PMID 9751059.
^ ^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. doi:10.1126/science.278.5339.866. PMID 9346485.
^ 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.
^ 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.
^ 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. PMC 232593. PMID 9372968.
^ 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.
^ ^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.
^ 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.
^ ^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.
^ 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.
^ Fischle W, Verdin E, Greene WC (August 2001). "Duration of nuclear NF-kappaB action regulated by reversible acetylation". Science 293 (5535): 1653–7. doi:10.1126/science.1062374. PMID 11533489.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

External links

OMIM entries on Ectodermal Dysplasia, Anhidrotic, with T-cell Immunodeficiency
NFKBIA protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
NF-kappaB inhibitor alpha at the US National Library of Medicine Medical Subject Headings (MeSH)

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English Journal

Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells.

McAdam E1, Haboubi HN, Griffiths AP, Baxter JN, Spencer-Harty S, Davies C, Jenkins GJ.
International journal of cancer. Journal international du cancer.Int J Cancer.2015 Feb 1;136(3):527-35. doi: 10.1002/ijc.29029. Epub 2014 Jun 23.
Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. Howeve
PMID 24931696

RNA interference screening identifies lenalidomide sensitizers in multiple myeloma, including RSK2.

Zhu YX1, Yin H2, Bruins LA1, Shi CX1, Jedlowski P1, Aziz M2, Sereduk C2, Kortuem KM1, Schmidt JE1, Champion M1, Braggio E1, Keith Stewart A1.
Blood.Blood.2015 Jan 15;125(3):483-91. doi: 10.1182/blood-2014-05-577130. Epub 2014 Nov 13.
To identify molecular targets that modify sensitivity to lenalidomide, we measured proliferation in multiple myeloma (MM) cells transfected with 27 968 small interfering RNAs in the presence of increasing concentrations of drug and identified 63 genes that enhance activity of lenalidomide upon sil
PMID 25395420

Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone.

Cheng SM1, Lin WH1, Lin CS1, Ho LJ2, Tsai TN1, Wu CH1, Lai JH3, Yang SP4.
Experimental biology and medicine (Maywood, N.J.).Exp Biol Med (Maywood).2015 Jan;240(1):99-108. doi: 10.1177/1535370214544263. Epub 2014 Jul 29.
Amiodarone, a common and effective antiarrhythmic drug, has been reported to have anti-inflammatory effects such as reducing the activation and movement of neutrophils. However, its effects on human T cells remain unclear. The aim of this study was to elucidate the effects and possible underlying me
PMID 25073960

Japanese Journal

Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration

Shinohara Masahiro,Adachi Yoshifumi,Mitsushita Junji,Kuwabara Mitsuhiro,Nagasawa Atsushi,Harada Saori,Furuta Shuichi,Zhang Yugen,Seheli Kajla,Miyazaki Hitoshi,Kamata Tohru
JOURNAL OF BIOLOGICAL CHEMISTRY 285(7), 4481-4488, 2010-02-12
… Diphenyleneiodonium (DPI) or Nox1 siRNAs blocked up-regulation of matrix metalloprotease-9 at both protein and mRNA levels in K-Ras-transformed normal rat kidney cells. … Furthermore, DPI and Nox1 siRNAs inhibited the activation of IKK alpha kinase and the degradation of I kappa B alpha, suppressing the NF kappa B-dependent matrix metalloprotease-9 promoter activity. …
NAID 120002696305

Sequence Fourier Analysis of a Specific Protein–DNA (RNA) Interaction; an Intermolecular Frequency Symmetry

Numao Naganori,Kamimoto Yoshihito
CHEMICAL & PHARMACEUTICAL BULLETIN 57(11), 1305-1307, 2009
… that a specific protein–DNA (RNA) interaction between p53 protein and divergent I kappa B kinase interacting protein (IKIP)-Apaf1 DNA promoter region, and between poliovirus 3CD protein and the 5′ terminal region of the RNA sequence can be successfully elucidated with a sequence Fourier analysis, alike various specific protein–protein interactions …
NAID 130000124830

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★リンクテーブル★

リンク元	「IκBタンパク質」「κB阻害因子」「I-kappa B」
関連記事	「B」「I」「Id」「kappa」

「IκBタンパク質」

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
	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
List of PDB id codes
	1IKN, 1NFI
Identifiers
Symbols	NFKBIA ; IKBA; MAD-3; NFKBI
External IDs	OMIM: 164008 MGI: 104741 HomoloGene: 7863 ChEMBL: 2898 GeneCards: NFKBIA Gene
Gene ontology
Molecular function	• protein binding; • transcription factor binding; • nuclear localization sequence binding; • enzyme binding; • heat shock protein binding; • ubiquitin protein ligase binding; • protein complex binding; • identical protein binding; • NF-kappaB binding;
Cellular component	• nucleus; • cytoplasm; • cytosol; • plasma membrane; • I-kappaB/NF-kappaB complex;
Biological process	• protein import into nucleus, translocation; • stimulatory C-type lectin receptor signaling pathway; • toll-like receptor signaling pathway; • MyD88-dependent toll-like receptor signaling pathway; • MyD88-independent toll-like receptor signaling pathway; • apoptotic process; • cytoplasmic sequestering of NF-kappaB; • negative regulation of macrophage derived foam cell differentiation; • positive regulation of cholesterol efflux; • negative regulation of lipid storage; • viral process; • lipopolysaccharide-mediated signaling pathway; • negative regulation of NF-kappaB transcription factor activity; • positive regulation of cellular protein metabolic process; • positive regulation of type I interferon production; • response to muramyl dipeptide; • toll-like receptor 2 signaling pathway; • toll-like receptor 3 signaling pathway; • toll-like receptor 4 signaling pathway; • toll-like receptor 5 signaling pathway; • toll-like receptor 9 signaling pathway; • toll-like receptor 10 signaling pathway; • TRIF-dependent toll-like receptor signaling pathway; • response to muscle stretch; • Fc-epsilon receptor signaling pathway; • toll-like receptor TLR1:TLR2 signaling pathway; • toll-like receptor TLR6:TLR2 signaling pathway; • regulation of cell proliferation; • regulation of NF-kappaB import into nucleus; • cytoplasmic sequestering of transcription factor; • negative regulation of apoptotic process; • response to exogenous dsRNA; • negative regulation of DNA binding; • innate immune response; • negative regulation of myeloid cell differentiation; • negative regulation of Notch signaling pathway; • positive regulation of transcription from RNA polymerase II promoter; • neurotrophin TRK receptor signaling pathway; • T cell receptor signaling pathway; • positive regulation of NF-kappaB transcription factor activity; • cellular response to cold; • nucleotide-binding oligomerization domain containing 1 signaling pathway; • nucleotide-binding oligomerization domain containing 2 signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;