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词条 IKBKG
释义

  1. Function

  2. Clinical significance

  3. As a drug target

  4. Interactions

  5. References

  6. Further reading

  7. External links

{{Infobox_gene}}

NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase complex that activates NF-κB.[1] The human gene for IKBKG is located on chromosome Xq28.[2] Multiple transcript variants encoding different isoforms have been found for this gene.

Function

{{main|IκB kinase}}

NEMO (IKK-γ) is the regulatory subunit of the inhibitor of IκB kinase (IKK) complex, which activates NF-κB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways.

Clinical significance

Mutations in the IKBKG gene results in incontinentia pigmenti,[3] hypohidrotic ectodermal dysplasia,[4] and several other types of immunodeficiencies.

Incontinentia Pigmenti (IP) is an X-linked dominant disease caused by a mutation in the IKBKG gene. Since IKBKG helps activate NF-κB, which protects cells against TNF-alpha induced apoptosis, a lack of IKBKG (and hence a lack of active NF-κB) makes cells more prone to apoptosis.

Moreover, NEMO has been shown to play a role in preeclampsia and may offer insights into the genetic etiology of this condition. An increased level of NEMO gene expression was found in the blood of pregnant women with preeclampsia and their children.[5] However, a decrease of the mRNA levels of total NEMO and the transcripts 1A, 1B, and 1C in placentas derived from preeclamptic women may be the main reason for intensified apoptosis.[5] Sanger sequencing has indicated two distinct variations in the 3’ UTR region of the NEMO gene in preeclamptic women (IKBKG:c.*368C>A and IKBKG:c.*402C>T).[6] The occurrence of a maternal TT genotype and either a TT genotype in the daughter or T allele in the son increases the risk of preeclampsia by 2.59 fold. The configuration of those maternal and fetal genotypes (TT mother/TT daughter or TT mother/T son) is also associated with the level of NEMO gene expression.[6]

NEMO deficiency syndrome is a rare genetic condition relating to a fault in IKBKG. It mostly affects males and has a highly variable set of symptoms and prognoses.[7]

As a drug target

A drug called NEMO Binding Domain (NBD) has been designed to inhibit activation of NF-κB.[10] NBD is a peptide that acts by binding to regulatory subunit NEMO (IKK-γ) thereby preventing it from binding subunits IKK-α and IKK-β and activating the IKK complex. In the absence of regulatory subunit IKK-γ the IKK complex is inactive, preventing the downstream signal transduction cascade leading to NF-κB activation. Binding of IKK-γ to IKK-α and IKK-β subunits activates the IKK complex leading to phosphorylation of IκB kinase, IκBα, and release of NF-κB dimers p105 and RELA to translocate to the nucleus and activate transcription of NF-κB responsive genes. In the presence of the NBD peptide, the IKK complex remains inactive and IκBα sequesters NF-κB dimers in the cytoplasm inhibiting transcription of NF-κB responsive genes. While NF-κB inhibitory drugs have previously been attractive to disease such as chronic inflammation and diabetes, specific cancers have been shown to have constitutive NF-κB activity.[11] Advanced B-cell lymphoma (ABC), a subtype of Diffuse large B-cell lymphoma (DLBCL) has been shown to have fundamental and upregulated NF-κB activity.[8] ABC lymphoma also has the lowest survival rate compared to DLBCL subtypes, Germinal Center B-cell-like and Undefined Type 3 lymphoma, highlighting the great clinical need to define targets for cancer therapy.[8] Notably, the NBD peptide targets the inflammation induced NF-κB activation pathway sparing the protective functions of basal NF-κB activity allowing for greater therapeutic value and fewer undesired side effects.

The NBD peptide was designed by identifying the amino acid binding sequence on IKK-α and IKK-β to which NEMO binds.[10] A small region on the carboxyl terminus of IKK-α (L738-L743) and IKK-β (L737-L742) is essential for a stable interaction with NEMO and for the assembly of the active IKK complex. Henceforth this region is called the NEMO binding domain (NBD). The NBD peptide consists of the region from T735 to E745 of the IKK-β subunit fused with a sequence derived from the Antennapedia homeodomain that mediates membrane translocation. Furthermore, wild type NBD peptide has been shown to dose-dependently inhibit interaction of IKKB with NEMO compared to mutant controls.[9] Additionally, NF-κB activation was suppressed in HeLa cells after incubation with NBD wild type peptides.[9] Moreover, to better understand the potential efficacy of the NBD peptide in suppressing inflammation, NBD peptide was tested on collagen induced rheumatoid arthritis mouse models. Notably, aberrant NF-κB activity is strongly associated with many aspects of the pathology of rheumatoid arthritis. Mice injected with wild-type NBD peptide showed only slightly visual signs of paw and joint swelling whereas mice injected with PBS or mutant NBD control peptides developed severe joint inflammation.[10] Additionally, analysis of the number of osteoclasts present in the joints of rheumatoid arthritic showed to be more prevalent in mice treated with PBS or the mutant NBD peptide compared to the NBD wild type peptide.[10] Markedly, throughout the mouse model studies neither toxicity or lethality nor damage to kidneys or livers, was observed.

Despite the potential for NBD peptide as a viable NF- κB inhibitory drug, disadvantages arise because of its peptide form. Peptides as drugs lack membrane permeability, are poorly orally viable, and generally have lower metabolic stability than small molecule drugs.[11] Therefore, the NBD peptide is unable to be an orally available compound and must be administered either intravenously or via intraperitoneal injection.

Interactions

IKBKG has been shown to interact with:

{{div col|colwidth=20em}}
  • BCL10,[12]
  • CDC37,[13][22]
  • CHUK[22][14][25][26] and
  • IKK2,[15][16][17][18][19]
  • IRAK1,[20][21]
  • NCOA3,[19]
  • PPM1B,[22]
  • TANK,[18]
  • TNFAIP3,[23]
  • TRAF3IP2,[24][25] and
  • TRAF6.[21][26]
{{Div col end}}{{clear}}

References

1. ^{{cite journal | vauthors = Rothwarf DM, Zandi E, Natoli G, Karin M | title = IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex | journal = Nature | volume = 395 | issue = 6699 | pages = 297–300 | date = September 1998 | pmid = 9751060 | doi = 10.1038/26261 }}
2. ^{{cite journal | vauthors = Jin DY, Jeang KT | title = Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28 | journal = Journal of Biomedical Science | volume = 6 | issue = 2 | pages = 115–20 | year = 1999 | pmid = 10087442 | doi = 10.1159/000025378 }}
3. ^{{cite journal | vauthors = Aradhya S, Woffendin H, Jakins T, Bardaro T, Esposito T, Smahi A, Shaw C, Levy M, Munnich A, D'Urso M, Lewis RA, Kenwrick S, Nelson DL | title = A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations | journal = Human Molecular Genetics | volume = 10 | issue = 19 | pages = 2171–9 | date = September 2001 | pmid = 11590134 | doi = 10.1093/hmg/10.19.2171 }}
4. ^{{cite journal | vauthors = Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, Shapira SK, Farndon PA, Wara DW, Emmal SA, Ferguson BM | title = A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO) | journal = American Journal of Human Genetics | volume = 67 | issue = 6 | pages = 1555–62 | date = December 2000 | pmid = 11047757 | pmc = 1287930 | doi = 10.1086/316914 }}
5. ^1 {{cite journal | vauthors = Sakowicz A, Hejduk P, Pietrucha T, et al.| title = Finding NEMO in preeclampsia | journal = Am J Obstet Gynecol| volume = 214 | issue = 4 | pages = 538.e1–538.e7 | date = 2016| doi =10.1016/j.ajog.2015.11.002 | pmid = 26571191 }}
6. ^1  
7. ^NEMO deficiency syndrome information, Great Ormond Street Hospital for Children
8. ^1 2 {{cite journal | vauthors = Nogai H, Wenzel SS, Hailfinger S, Grau M, Kaergel E, Seitz V, Wollert-Wulf B, Pfeifer M, Wolf A, Frick M, Dietze K, Madle H, Tzankov A, Hummel M, Dörken B, Scheidereit C, Janz M, Lenz P, Thome M, Lenz G | title = IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL | journal = Blood | volume = 122 | issue = 13 | pages = 2242–50 | date = September 2013 | pmid = 23869088 | doi = 10.1182/blood-2013-06-508028 }}
9. ^1 2 3 {{cite journal | vauthors = May MJ, D'Acquisto F, Madge LA, Glöckner J, Pober JS, Ghosh S | title = Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex | journal = Science | volume = 289 | issue = 5484 | pages = 1550–4 | date = September 2000 | pmid = 10968790 | doi = 10.1126/science.289.5484.1550 }}
10. ^1 {{cite journal | vauthors = Strickland I, Ghosh S | title = Use of cell permeable NBD peptides for suppression of inflammation | journal = Annals of the Rheumatic Diseases | volume = 65 Suppl 3 | pages = iii75–82 | date = November 2006 | pmid = 17038479 | doi = 10.1136/ard.2006.058438 | pmc=1798375}}
11. ^{{cite journal | vauthors = Craik DJ, Fairlie DP, Liras S, Price D | title = The future of peptide-based drugs | journal = Chemical Biology & Drug Design | volume = 81 | issue = 1 | pages = 136–47 | date = January 2013 | pmid = 23253135 | doi = 10.1111/cbdd.12055 }}
12. ^{{cite journal | vauthors = Wu CJ, Ashwell JD | title = NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 8 | pages = 3023–8 | date = February 2008 | pmid = 18287044 | pmc = 2268578 | doi = 10.1073/pnas.0712313105 }}
13. ^{{cite journal | vauthors = Hayden MS, Ghosh S | title = Keeping cartographers busy | journal = Nature Cell Biology | volume = 6 | issue = 2 | pages = 87–9 | date = February 2004 | pmid = 14755267 | doi = 10.1038/ncb0204-87 }}
14. ^{{cite journal | vauthors = Agou F, Ye F, Goffinont S, Courtois G, Yamaoka S, Israël A, Véron M | title = NEMO trimerizes through its coiled-coil C-terminal domain | journal = The Journal of Biological Chemistry | volume = 277 | issue = 20 | pages = 17464–75 | date = May 2002 | pmid = 11877453 | doi = 10.1074/jbc.M201964200 }}
15. ^1 2 {{cite journal | vauthors = Chen G, Cao P, Goeddel DV | title = TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90 | journal = Molecular Cell | volume = 9 | issue = 2 | pages = 401–10 | date = February 2002 | pmid = 11864612 | doi = 10.1016/s1097-2765(02)00450-1 }}
16. ^1 {{cite journal | vauthors = Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ | title = Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain | journal = Cell | volume = 103 | issue = 2 | pages = 351–61 | date = October 2000 | pmid = 11057907 | doi = 10.1016/s0092-8674(00)00126-4 }}
17. ^1 {{cite journal | vauthors = Shifera AS, Horwitz MS | title = Mutations in the zinc finger domain of IKK gamma block the activation of NF-kappa B and the induction of IL-2 in stimulated T lymphocytes | journal = Molecular Immunology | volume = 45 | issue = 6 | pages = 1633–45 | date = March 2008 | pmid = 18207244 | doi = 10.1016/j.molimm.2007.09.036 }}
18. ^1 {{cite journal | vauthors = Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U | title = Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases | journal = The Journal of Biological Chemistry | volume = 277 | issue = 40 | pages = 37029–36 | date = October 2002 | pmid = 12133833 | doi = 10.1074/jbc.M205069200 }}
19. ^1 {{cite journal | vauthors = Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW | title = Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase | journal = Molecular and Cellular Biology | volume = 22 | issue = 10 | pages = 3549–61 | date = May 2002 | pmid = 11971985 | pmc = 133790 | doi = 10.1128/mcb.22.10.3549-3561.2002 }}
20. ^{{cite journal | vauthors = Conze DB, Wu CJ, Thomas JA, Landstrom A, Ashwell JD | title = Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation | journal = Molecular and Cellular Biology | volume = 28 | issue = 10 | pages = 3538–47 | date = May 2008 | pmid = 18347055 | pmc = 2423148 | doi = 10.1128/MCB.02098-07 }}
21. ^1 {{cite journal | vauthors = Windheim M, Stafford M, Peggie M, Cohen P | title = Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase | journal = Molecular and Cellular Biology | volume = 28 | issue = 5 | pages = 1783–91 | date = March 2008 | pmid = 18180283 | pmc = 2258775 | doi = 10.1128/MCB.02380-06 }}
22. ^{{cite journal | vauthors = Prajapati S, Verma U, Yamamoto Y, Kwak YT, Gaynor RB | title = Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity | journal = The Journal of Biological Chemistry | volume = 279 | issue = 3 | pages = 1739–46 | date = January 2004 | pmid = 14585847 | doi = 10.1074/jbc.M306273200 }}
23. ^{{cite journal | vauthors = Zhang SQ, Kovalenko A, Cantarella G, Wallach D | title = Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation | journal = Immunity | volume = 12 | issue = 3 | pages = 301–11 | date = March 2000 | pmid = 10755617 | doi = 10.1016/S1074-7613(00)80183-1 }}
24. ^{{cite journal | vauthors = Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U | title = CIKS, a connection to Ikappa B kinase and stress-activated protein kinase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 19 | pages = 10494–9 | date = September 2000 | pmid = 10962033 | pmc = 27052 | doi = 10.1073/pnas.190245697 }}
25. ^{{cite journal | vauthors = Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR | title = Act1, an NF-kappa B-activating protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 19 | pages = 10489–93 | date = September 2000 | pmid = 10962024 | pmc = 27051 | doi = 10.1073/pnas.160265197 }}
26. ^{{cite journal | vauthors = Lamothe B, Campos AD, Webster WK, Gopinathan A, Hur L, Darnay BG | title = The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL | journal = The Journal of Biological Chemistry | volume = 283 | issue = 36 | pages = 24871–80 | date = September 2008 | pmid = 18617513 | pmc = 2529010 | doi = 10.1074/jbc.M802749200 }}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Rothwarf DM, Zandi E, Natoli G, Karin M | title = IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex | journal = Nature | volume = 395 | issue = 6699 | pages = 297–300 | date = September 1998 | pmid = 9751060 | doi = 10.1038/26261 }}
  • {{cite journal | vauthors = Mercurio F, Murray BW, Shevchenko A, Bennett BL, Young DB, Li JW, Pascual G, Motiwala A, Zhu H, Mann M, Manning AM | title = IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex | journal = Molecular and Cellular Biology | volume = 19 | issue = 2 | pages = 1526–38 | date = February 1999 | pmid = 9891086 | pmc = 116081 | doi = 10.1128/mcb.19.2.1526 }}
  • {{cite journal | vauthors = Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, Wallach D, Horwitz MS | title = Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 3 | pages = 1042–7 | date = February 1999 | pmid = 9927690 | pmc = 15347 | doi = 10.1073/pnas.96.3.1042 }}
  • {{cite journal | vauthors = Jin DY, Jeang KT | title = Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28 | journal = Journal of Biomedical Science | volume = 6 | issue = 2 | pages = 115–20 | year = 1999 | pmid = 10087442 | doi = 10.1159/000025378 }}
  • {{cite journal | vauthors = Jin DY, Giordano V, Kibler KV, Nakano H, Jeang KT | title = Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma | journal = The Journal of Biological Chemistry | volume = 274 | issue = 25 | pages = 17402–5 | date = June 1999 | pmid = 10364167 | doi = 10.1074/jbc.274.25.17402 }}
  • {{cite journal | vauthors = Zhang SQ, Kovalenko A, Cantarella G, Wallach D | title = Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation | journal = Immunity | volume = 12 | issue = 3 | pages = 301–11 | date = March 2000 | pmid = 10755617 | doi = 10.1016/S1074-7613(00)80183-1 }}
  • {{cite journal | vauthors = Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, Israël A, Heiss NS, Klauck SM, Kioschis P, Wiemann S, Poustka A, Esposito T, Bardaro T, Gianfrancesco F, Ciccodicola A, D'Urso M, Woffendin H, Jakins T, Donnai D, Stewart H, Kenwrick SJ, Aradhya S, Yamagata T, Levy M, Lewis RA, Nelson DL | title = Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium | journal = Nature | volume = 405 | issue = 6785 | pages = 466–72 | date = May 2000 | pmid = 10839543 | doi = 10.1038/35013114 }}
  • {{cite journal | vauthors = Inohara N, Koseki T, Lin J, del Peso L, Lucas PC, Chen FF, Ogura Y, Núñez G | title = An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways | journal = The Journal of Biological Chemistry | volume = 275 | issue = 36 | pages = 27823–31 | date = September 2000 | pmid = 10880512 | doi = 10.1074/jbc.M003415200 }}
  • {{cite journal | vauthors = Ye Z, Connor JR | title = cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs | journal = Biochemical and Biophysical Research Communications | volume = 275 | issue = 1 | pages = 223–7 | date = August 2000 | pmid = 10944468 | doi = 10.1006/bbrc.2000.3282 }}
  • {{cite journal | vauthors = Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR | title = Act1, an NF-kappa B-activating protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 19 | pages = 10489–93 | date = September 2000 | pmid = 10962024 | pmc = 27051 | doi = 10.1073/pnas.160265197 }}
  • {{cite journal | vauthors = Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U | title = CIKS, a connection to Ikappa B kinase and stress-activated protein kinase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 19 | pages = 10494–9 | date = September 2000 | pmid = 10962033 | pmc = 27052 | doi = 10.1073/pnas.190245697 }}
  • {{cite journal | vauthors = May MJ, D'Acquisto F, Madge LA, Glöckner J, Pober JS, Ghosh S | title = Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex | journal = Science | volume = 289 | issue = 5484 | pages = 1550–4 | date = September 2000 | pmid = 10968790 | doi = 10.1126/science.289.5484.1550 }}
  • {{cite journal | vauthors = Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, Shapira SK, Farndon PA, Wara DW, Emmal SA, Ferguson BM | title = A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO) | journal = American Journal of Human Genetics | volume = 67 | issue = 6 | pages = 1555–62 | date = December 2000 | pmid = 11047757 | pmc = 1287930 | doi = 10.1086/316914 }}
  • {{cite journal | vauthors = Xiao G, Sun SC | title = Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein | journal = Oncogene | volume = 19 | issue = 45 | pages = 5198–203 | date = October 2000 | pmid = 11064457 | doi = 10.1038/sj.onc.1203894 }}
  • {{cite journal | vauthors = Li XH, Fang X, Gaynor RB | title = Role of IKKgamma/nemo in assembly of the Ikappa B kinase complex | journal = The Journal of Biological Chemistry | volume = 276 | issue = 6 | pages = 4494–500 | date = February 2001 | pmid = 11080499 | doi = 10.1074/jbc.M008353200 }}
  • {{cite journal | vauthors = Poyet JL, Srinivasula SM, Alnemri ES | title = vCLAP, a caspase-recruitment domain-containing protein of equine Herpesvirus-2, persistently activates the Ikappa B kinases through oligomerization of IKKgamma | journal = The Journal of Biological Chemistry | volume = 276 | issue = 5 | pages = 3183–7 | date = February 2001 | pmid = 11113112 | doi = 10.1074/jbc.C000792200 }}
  • {{cite journal | vauthors = Jain A, Ma CA, Liu S, Brown M, Cohen J, Strober W | title = Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia | journal = Nature Immunology | volume = 2 | issue = 3 | pages = 223–8 | date = March 2001 | pmid = 11224521 | doi = 10.1038/85277 }}
  • {{cite journal | vauthors = Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, Le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, Israël A, Courtois G, Casanova JL | title = X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling | journal = Nature Genetics | volume = 27 | issue = 3 | pages = 277–85 | date = March 2001 | pmid = 11242109 | doi = 10.1038/85837 }}
  • {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–92 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
  • {{cite journal | vauthors = Galgóczy P, Rosenthal A, Platzer M | title = Human-mouse comparative sequence analysis of the NEMO gene reveals an alternative promoter within the neighboring G6PD gene | journal = Gene | volume = 271 | issue = 1 | pages = 93–8 | date = June 2001 | pmid = 11410370 | doi = 10.1016/S0378-1119(01)00492-9 }}
{{refend}}

External links

  • {{MeshName|IKBKG+protein,+human}}
  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=i-p GeneReviews/NIH/NCBI/UW entry on Incontinentia Pigmenti]
  • [https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300248 OMIM IKBKG]
  • [https://www.ncbi.nlm.nih.gov/books/NBK1378/ GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview]
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