Genomes and Genes
Gene Symbol: IkappaBalpha
Description: NFKB inhibitor alpha
Alias: IKBA, MAD-3, NFKBI, NF-kappa-B inhibitor alpha, I-kappa-B-alpha, IkappaBalpha, ikB-alpha, major histocompatibility complex enhancer-binding protein MAD3, nuclear factor of kappa light chain gene enhancer in B-cells, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
- Abdallah A, Sato H, Grutters J, Veeraraghavan S, Lympany P, Ruven H, et al. Inhibitor kappa B-alpha (IkappaB-alpha) promoter polymorphisms in UK and Dutch sarcoidosis. Genes Immun. 2003;4:450-4 pubmed..01). The -826T allelic carriage did not show any association with lung function. These results indicate that the NF-kappaB activation pathway might be associated with the inflammation of sarcoidosis. ..
- Lang V, Janzen J, Fischer G, Soneji Y, Beinke S, Salmeron A, et al. betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932. Mol Cell Biol. 2003;23:402-13 pubmed..resides in a conserved motif (Asp-Ser(927)-Gly-Val-Glu-Thr-Ser(932)) homologous to the IKK target sequence in IkappaBalpha. In this study, TNF-alpha-induced p105 proteolysis was revealed to additionally require the phosphorylation of ..
- Bu H, Rosdahl I, Sun X, Zhang H. Importance of polymorphisms in NF-kappaB1 and NF-kappaBIalpha genes for melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients. J Cancer Res Clin Oncol. 2007;133:859-66 pubmed..NF-kappaB1 and NF-kappaBIalpha genes might be susceptible genes for melanoma risk and functional polymorphisms of these genes might be biological predictors for melanoma progression. ..
- Carbia Nagashima A, Gerez J, Perez Castro C, Paez Pereda M, Silberstein S, Stalla G, et al. RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell. 2007;131:309-23 pubmed..Together, these findings point to a central role of RSUME in the regulation of sumoylation and, hence, several critical regulatory pathways in mammalian cells. ..
- Chang E, Birmann B, Kasperzyk J, Conti D, Kraft P, Ambinder R, et al. Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2009;18:976-86 pubmed publisher..In conclusion, genetic variation in the NF-kappaB pathway seems to influence risk of HL. Pooled studies are needed to detect any heterogeneity in the association with NF-kappaB across HL subgroups, including aspirin users and nonusers. ..
- Vitagliano L, Fiume G, Scognamiglio P, Doti N, Cannavò R, Puca A, et al. Structural and functional insights into I?B-?/HIV-1 Tat interaction. Biochimie. 2011;93:1592-600 pubmed publisher..These findings have been corroborated by mutagenesis studies on the full-length I?B-?, which unveil that different I?B-? residues are involved in NF-?B or Tat recognition. ..
- Lake A, Shield L, Cordano P, Chui D, Osborne J, Crae S, et al. Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases. Int J Cancer. 2009;125:1334-42 pubmed publisher..It remains possible that defects in genes encoding other inhibitors of NF-kappaB, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series. ..
- Aillet F, Lopitz Otsoa F, Egaña I, Hjerpe R, Fraser P, Hay R, et al. Heterologous SUMO-2/3-ubiquitin chains optimize I?B? degradation and NF-?B activity. PLoS ONE. 2012;7:e51672 pubmed publisher..Thus, hybrid SUMO-2/3-ubiquitin chains increase the susceptibility of modified I?B? to the action of 26S proteasome, contributing to the optimal control of NF-?B activity after TNF?-stimulation. ..
- He Y, Zhang H, Yin J, Xie J, Tan X, Liu S, et al. IkappaBalpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C. Carcinogenesis. 2009;30:1916-22 pubmed publisher..associations of the polymorphisms within the promoter regions of NFKB1 encoding NF-kappaB1 and NFKBIA encoding IkappaBalpha with the development of HCC...
- Ou T, Lin C, Lin Y, Li R, Tsai W, Liu H, et al. IkappaBalpha promoter polymorphisms in patients with primary Sjögren's syndrome. J Clin Immunol. 2008;28:440-4 pubmed publisher..The IkappaBalpha -881 A/G, IkappaBalpha -826 C/T, IkappaBalpha -550 A/T, IkappaBalpha -519 C/T, and IkappaBalpha -297 C/T ..
- Palmieri C, Trimboli F, Puca A, Fiume G, Scala G, Quinto I. Inhibition of HIV-1 replication in primary human monocytes by the IkappaB-alphaS32/36A repressor of NF-kappaB. Retrovirology. 2004;1:45 pubmed
- Li C, Chen S, Yue P, Deng X, Lonial S, Khuri F, et al. Proteasome inhibitor PS-341 (bortezomib) induces calpain-dependent IkappaB(alpha) degradation. J Biol Chem. 2010;285:16096-104 pubmed publisher..Collectively, these unexpected findings suggest not only a novel paradigm regarding the relationship between proteasome inhibition and NF-kappaB activity but also a strategy to enhance the anticancer efficacy of PS-341. ..
- Shin D, Li S, Yang S, Lee B, Lee M, Park J. Inhibitor of nuclear factor-kappaB alpha derepresses hypoxia-inducible factor-1 during moderate hypoxia by sequestering factor inhibiting hypoxia-inducible factor from hypoxia-inducible factor 1alpha. FEBS J. 2009;276:3470-80 pubmed publisher..Therefore, IkappaB alpha, owing to its interactions with NF-kappaB and HIF-1alpha, may play a pivotal role in the crosstalk between the molecular events that underlie inflammatory and hypoxic responses. ..
- Gao J, Pfeifer D, He L, Qiao F, Zhang Z, Arbman G, et al. Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol. 2007;42:345-50 pubmed..study was to investigate the susceptibility of an A to G variation (rs696) in the 3' UTR of NFKBIA (encoding IkappaBalpha) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC ..
- Lin C, Ou T, Wu C, Tsai W, Liu H, Yen J. IkappaBalpha promoter polymorphisms in patients with rheumatoid arthritis. Int J Immunogenet. 2007;34:51-4 pubmed..The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length ..
- White K, Vierkant R, Phelan C, Fridley B, Anderson S, Knutson K, et al. Polymorphisms in NF-kappaB inhibitors and risk of epithelial ovarian cancer. BMC Cancer. 2009;9:170 pubmed publisher..the association between single nucleotide polymorphisms (SNPs) in NFKBIA and NFKBIB (the genes encoding IkappaBalpha and IkappaBbeta, respectively) and risk of epithelial ovarian cancer...
- Bredel M, Scholtens D, Yadav A, Alvarez A, Renfrow J, Chandler J, et al. NFKBIA deletion in glioblastomas. N Engl J Med. 2011;364:627-37 pubmed publisher..Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival. ..
- Spink C, Gray L, Davies F, Morgan G, Bidwell J. Haplotypic structure across the I kappa B alpha gene (NFKBIA) and association with multiple myeloma. Cancer Lett. 2007;246:92-9 pubmed..The NFKBIA gene product, IkappaBalpha, binds to NF-kappaB preventing its activation and is important in mediating resistance to apoptosis in B-cell ..
- Wang S, Tian L, Zeng Z, Zhang M, Wu K, Chen M, et al. IkappaBalpha polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese. BMC Gastroenterol. 2010;10:15 pubmed publisher..I kappaB alpha rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population. ..
- Cheng C, Su J, Lin C, Su C, Shih C, Yang S, et al. Effects of NFKB1 and NFKBIA gene polymorphisms on hepatocellular carcinoma susceptibility and clinicopathological features. PLoS ONE. 2013;8:e56130 pubmed publisher..Our results indicate that the NFKB1 -94 Ins promoter polymorphism increased the risk of HCC, and may be applied as a predictive factor for the clinical stage and tumor size in female HCC patients. ..
- Kim L, Shin H, Park B, Jung J, Kim J, Kim Y, et al. Identification of variants in NFKBIA and association analysis with hepatocellular carcinoma risk among chronic HBV patients. Hum Mutat. 2003;21:652-3 pubmedHuman nuclear factor of kappa light chain gene enhancer in B cells inhibitor, alpha (NFKBIA) inhibits the action of NF-kappaB by forming a heterodimer with NF-kappaB, and preventing its translocation to the nucleus...
- Klein W, Tromm A, Folwaczny C, Hagedorn M, Duerig N, Epplen J, et al. A polymorphism of the NFKBIA gene is associated with Crohn's disease patients lacking a predisposing allele of the CARD15 gene. Int J Colorectal Dis. 2004;19:153-6 pubmed..The findings indicate that the phenotype Crohn's disease is to be substructured with respect to genetic susceptibility. ..
- Fan C, Li Q, Ross D, Engelhardt J. Tyrosine phosphorylation of I kappa B alpha activates NF kappa B through a redox-regulated and c-Src-dependent mechanism following hypoxia/reoxygenation. J Biol Chem. 2003;278:2072-80 pubmed..Tyrosine 42 phosphorylation of I kappa B alpha has been shown to mediate NF kappa B activation following hypoxia/reoxygenation (H/R) or pervanadate ..
- Da Silva Ferrada E, Torres Ramos M, Aillet F, Campagna M, Matute C, Rivas C, et al. Role of monoubiquitylation on the control of I?B? degradation and NF-?B activity. PLoS ONE. 2011;6:e25397 pubmed publisher..Such pool of I?B? may play an important role in the control of basal and signal-mediated NF-?B activity. ..
- Curran J, Weinstein S, Griffiths L. Polymorphic variants of NFKB1 and its inhibitory protein NFKBIA, and their involvement in sporadic breast cancer. Cancer Lett. 2002;188:103-7 pubmed..Results do not support an involvement of the tested NFKB1 and NFKBIA polymorphisms in susceptibility to sporadic breast cancer, in the tested Caucasian population. ..
- Taylor J, Bren G, Pennington K, Trushin S, Asin S, Paya C. Serine 32 and serine 36 of IkappaBalpha are directly phosphorylated by protein kinase CKII in vitro. J Mol Biol. 1999;290:839-50 pubmedb>IkappaBalpha is an inherently unstable protein which binds to and retains the ubiquitous transcription factor NFkappaB in the cytoplasm of resting cells...
- Chen Lf -, Fischle W, Verdin E, Greene W. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science. 2001;293:1653-7 pubmed..regulate the termination of nuclear NF-kappaB action remain poorly defined, although the activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a key role...
- Lin C, Wang S, Ou T, Li R, Tsai W, Liu H, et al. I kappa B alpha promoter polymorphisms in patients with systemic lupus erythematosus. J Clin Immunol. 2008;28:207-13 pubmedTo investigate the associations of IkappaBalpha gene polymorphisms with the development and clinical manifestations of systemic lupus erythematosus (SLE), 110 patients with SLE and 120 unrelated healthy controls were enrolled in this ..
- Lin C, Hsieh Y, Hsin C, Su C, Lin C, Wei L, et al. Effects of NFKB1 and NFKBIA gene polymorphisms on susceptibility to environmental factors and the clinicopathologic development of oral cancer. PLoS ONE. 2012;7:e35078 pubmed publisher..examines associations between polymorphisms within promoter regions of NFKB1 encoding NF-?B1 and NFKBIA encoding IkappaBalpha (I?B?) with both the susceptibility to develop OSCC and the clinicopathological characteristics of the tumors.
- Liu X, Yu H, Yang W, Zhou X, Lu H, Shi D. Mutations of NFKBIA in biopsy specimens from Hodgkin lymphoma. Cancer Genet Cytogenet. 2010;197:152-7 pubmed publisher..Compared with reactive surrounding lymphocytes, inhibitor kappaBalpha protein (IkappaBalpha) expression was weaker in the cytoplasm of H-RS (Hodgkin and Reed-Sternberg) cells...
- Busino L, Millman S, Scotto L, Kyratsous C, Basrur V, O CONNOR O, et al. Fbxw7?- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nat Cell Biol. 2012;14:375-85 pubmed publisher..Thus, in multiple myeloma, Fbxw7? and GSK3 function as pro-survival factors through the control of p100 degradation. ..
- Jungnickel B, Staratschek Jox A, Bräuninger A, Spieker T, Wolf J, Diehl V, et al. Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma. J Exp Med. 2000;191:395-402 pubmed..cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IkappaBalpha gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a ..
- Liu Q, Li J, Khoury J, Colgan S, Ibla J. Adenosine signaling mediates SUMO-1 modification of IkappaBalpha during hypoxia and reoxygenation. J Biol Chem. 2009;284:13686-95 pubmed publisherSmall ubiquitin-like modifier 1 (SUMO-1) modification of IkappaBalpha has been described to actively participate in NFkappaB regulation...
- Prigent M, Barlat I, Langen H, Dargemont C. 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. 2000;275:36441-9 pubmedb>IkappaBalpha inhibits the transcriptional activity of NF-kappaB both in the cytoplasm by preventing the nuclear translocation of NF-kappaB and in the nucleus where it dissociates NF-kappaB from DNA and transports it back to the cytoplasm...
- Szamosi T, Lakatos P, Szilvasi A, Lakatos L, Kovacs A, Molnar T, et al. The 3'UTR NFKBIA variant is associated with extensive colitis in Hungarian IBD patients. Dig Dis Sci. 2009;54:351-9 pubmed publisher..The NFKBIA 3'UTR GG genotype was associated with an increased risk for extensive colitis in Hungarian patients. In contrast, variant alleles did not predict response to medical therapy or need for surgery. ..
- Bour S, Perrin C, Akari H, Strebel K. The human immunodeficiency virus type 1 Vpu protein inhibits NF-kappa B activation by interfering with beta TrCP-mediated degradation of Ikappa B. J Biol Chem. 2001;276:15920-8 pubmed..However, in the presence of Vpu, this HIV-mediated NF-kappaB activation was markedly reduced. These results suggest that Vpu modulates both virus- and cytokine-induced activation of NF-kappaB in HIV-1-infected cells. ..
- Truhlar S, Mathes E, Cervantes C, Ghosh G, Komives E. Pre-folding IkappaBalpha alters control of NF-kappaB signaling. J Mol Biol. 2008;380:67-82 pubmed publisher..b>IkappaBalpha binds to and inhibits the transcriptional activity of NF-kappaB via its ankyrin repeat (AR) domain...
- Park S, Huq M, Hu X, Wei L. Tyrosine nitration on p65: a novel mechanism to rapidly inactivate nuclear factor-kappaB. Mol Cell Proteomics. 2005;4:300-9 pubmed..Tyr nitration of p65 induced its dissociation from p50, its association with IkappaBalpha, and subsequent sequestration of p65 in the cytoplasm by IkappaBalpha-mediated export...
- Wan F, Anderson D, Barnitz R, Snow A, Bidere N, Zheng L, et al. Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. Cell. 2007;131:927-39 pubmed..Our observations provide insight into how NF-kappaB selectively controls gene expression. ..
- Xu G, Lo Y, Li Q, Napolitano G, Wu X, Jiang X, et al. Crystal structure of inhibitor of κB kinase β. Nature. 2011;472:325-30 pubmed publisher..Other IKK family members, IKKα, TBK1 and IKK-i, may have a similar trimodular architecture and function. ..
- Kiernan R, Brès V, Ng R, Coudart M, El Messaoudi S, Sardet C, et al. Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65. J Biol Chem. 2003;278:2758-66 pubmed..localization and consequently the transcriptional activity of NF-kappaB is tightly regulated by its partner IkappaBalpha. Here, we show that the p65 subunit of NF-kappaB is acetylated by both p300 and PCAF on lysines 122 and 123...
- Mahabeleshwar G, Kundu G. Syk, a protein-tyrosine kinase, suppresses the cell motility and nuclear factor kappa B-mediated secretion of urokinase type plasminogen activator by inhibiting the phosphatidylinositol 3'-kinase activity in breast cancer cells. J Biol Chem. 2003;278:6209-21 pubmed..PI 3'-kinase activity and stimulated the interaction between the inhibitor of nuclear factor kappa B alpha (I kappa B alpha) and the p85 alpha domain of PI 3'-kinase through tyrosine phosphorylation of the I kappa B alpha, which ..
- Courtois G, Smahi A, Reichenbach J, Doffinger R, Cancrini C, Bonnet M, et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest. 2003;112:1108-15 pubmed..an autosomal-dominant (AD) form of EDA-ID associated with a heterozygous missense mutation at serine 32 of IkappaBalpha. This mutation is gain-of-function, as it enhances the inhibitory capacity of IkappaBalpha by preventing its ..
- Osborne J, Lake A, Alexander F, Taylor G, Jarrett R. Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma. Int J Cancer. 2005;116:646-51 pubmedSomatic inactivation of NFKBIA, the gene encoding IkappaBalpha, is a frequent occurrence in the malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL)...
- Shah A, Verma A, Patel K, Noel R, Rivera Amill V, Silverstein P, et al. HIV-1 gp120 induces expression of IL-6 through a nuclear factor-kappa B-dependent mechanism: suppression by gp120 specific small interfering RNA. PLoS ONE. 2011;6:e21261 pubmed publisher..These results demonstrate that HIV-1 gp120-mediated over-expression of IL-6 in astrocytes is one mechanism responsible for neuroinflammation in HIV-infected individuals and this is mediated by the NF-?B pathway. ..
- Bergqvist S, Croy C, Kjaergaard M, Huxford T, Ghosh G, Komives E. Thermodynamics reveal that helix four in the NLS of NF-kappaB p65 anchors IkappaBalpha, forming a very stable complex. J Mol Biol. 2006;360:421-34 pubmedb>IkappaBalpha is an ankyrin repeat protein that inhibits NF-kappaB transcriptional activity by sequestering NF-kappaB outside of the nucleus in resting cells...
- Andersen V, Christensen J, Overvad K, Tjønneland A, Vogel U. Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes. BMC Cancer. 2010;10:484 pubmed publisher..A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology. ..
- Bossis G, Salinas S, Cartier C, Devaux C, Briant L. NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases. FEBS Lett. 2002;516:257-64 pubmed..Taken together, these results confirm that IKKs complex play a key role in gp120(env)-induced NF-kappaB activation. ..
- Lain de Lera T, Folgueira L, Martin A, Dargemont C, Pedraza M, Bermejo M, et al. Expression of IkappaBalpha in the nucleus of human peripheral blood T lymphocytes. Oncogene. 1999;18:1581-8 pubmed..Our results demonstrate that in resting and PMA-activated human PBL, I(kappa)B(alpha) is present in the nucleus in an apparently inactive form unable to disrupt NF-kappaB binding from DNA. ..
- Ninomiya Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999;398:252-6 pubmed..Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway. ..
- Crepieux P, Kwon H, Leclerc N, Spencer W, Richard S, Lin R, et al. I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain. Mol Cell Biol. 1997;17:7375-85 pubmed
- Brockman J, Scherer D, McKinsey T, Hall S, Qi X, Lee W, et al. Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation. Mol Cell Biol. 1995;15:2809-18 pubmed..activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-..
- Arenzana Seisdedos F, Thompson J, Rodriguez M, Bachelerie F, Thomas D, Hay R. Inducible nuclear expression of newly synthesized I kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-kappa B. Mol Cell Biol. 1995;15:2689-96 pubmed..The inhibitor protein I kappa B alpha maintains NF-kappa B in an inactive form in the cytoplasms of unstimulated cells, but upon cell activation, I ..
- Baeuerle P, Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988;242:540-6 pubmed..The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor. ..
- Chen Z, Hagler J, Palombella V, Melandri F, Scherer D, Ballard D, et al. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 1995;9:1586-97 pubmedThe transcription factor NF-kappa B is sequestered in the cytoplasm by the inhibitor protein I kappa B alpha. Extracellular inducers of NF-kappa B activate signal transduction pathways that result in the phosphorylation and subsequent ..
- Roulston A, Lin R, Beauparlant P, Wainberg M, Hiscott J. Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B/Rel transcription factors. Microbiol Rev. 1995;59:481-505 pubmed..Phosphorylation and degradation of the cytoplasmic inhibitor I kappa B alpha are crucial regulatory events in the activation of NF-kappa B DNA-binding activity...