Gene Symbol: IKKgamma
Description: inhibitor of nuclear factor kappa B kinase subunit gamma
Alias: AMCBX1, FIP-3, FIP3, Fip3p, IKK-gamma, IKKAP1, IKKG, IMD33, IP1, IP2, IPD2, NEMO, ZC2HC9, NF-kappa-B essential modulator, I-kappa-B kinase subunit gamma, NF-kappa-B essential modifier, ikB kinase subunit gamma, ikB kinase-associated protein 1, incontinentia pigmenti, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
Species: human
Products:     IKKgamma

Top Publications

  1. Aradhya S, Woffendin H, Jakins T, Bardaro T, Esposito T, Smahi A, et al. A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations. Hum Mol Genet. 2001;10:2171-9 pubmed
    b>Incontinentia pigmenti (IP) is an X-linked dominant disorder characterized by abnormal skin pigmentation, retinal detachment, anodontia, alopecia, nail dystrophy and central nervous system defects...
  2. Zhu G, Wu C, Zhao Y, Ashwell J. Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP. Curr Biol. 2007;17:1438-43 pubmed
    NF-kappaB essential modulator (NEMO), the regulatory subunit of the IkappaB kinase (IKK) that activates NF-kappaB, is essential for NF-kappaB activation...
  3. Mercurio F, Murray B, Shevchenko A, Bennett B, Young D, Li J, et al. IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex. Mol Cell Biol. 1999;19:1526-38 pubmed
    ..To this end, we purified and cloned a novel component common to both complexes, named IKK-associated protein 1 (IKKAP1). In vitro, IKKAP1 associated specifically with IKK2 but not IKK1...
  4. Janssens S, Tinel A, Lippens S, Tschopp J. PIDD mediates NF-kappaB activation in response to DNA damage. Cell. 2005;123:1079-92 pubmed
    ..stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappaB-activating kinase complex, NEMO, is formed...
  5. Doffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001;27:277-85 pubmed
    ..IKBKG encodes NEMO, the regulatory subunit of the IKK (IkappaB kinase) complex, which is essential for NF-kappaB signaling...
  6. Zhang S, Kovalenko A, Cantarella G, Wallach D. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity. 2000;12:301-11 pubmed
    ..Here we show that triggering of the p55 TNF receptor induces binding of RIP to NEMO (IKKgamma), a component of the I-kappa-B-kinase (IKK) "signalosome" complex, as well as recruitment of RIP to the ..
  7. Hacker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006;2006:re13 pubmed
    ..and IKKbeta molecules in the cell are part of IKK complexes that also contain a regulatory subunit called IKKgamma or NEMO...
  8. Wu C, Conze D, Li T, Srinivasula S, Ashwell J. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat Cell Biol. 2006;8:398-406 pubmed
    ..NEMO is essential for NF-kappaB activation, and NEMO dysfunction in humans is the cause of incontinentia pigmenti and hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID)...
  9. Shembade N, Harhaj N, Yamamoto M, Akira S, Harhaj E. The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation. J Virol. 2007;81:13735-42 pubmed
    ..Finally, the interaction of Tax with NEMO is disrupted in the absence of Tax ubiquitination and Ubc13 expression, suggesting that Tax ubiquitination is ..

More Information


  1. Nasr R, Chiari E, El Sabban M, Mahieux R, Kfoury Y, Abdulhay M, et al. Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-kappaB activation. Blood. 2006;107:4021-9 pubmed
    ..Thus, ubiquitylation and sumoylation of the same residues of Tax regulate 2 essential steps controlling NF-kappaB activation, demonstrating how these posttranslational modifications can cooperate to promote Tax-induced transformation...
  2. Windheim M, Stafford M, Peggie M, Cohen P. 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. Mol Cell Biol. 2008;28:1783-91 pubmed publisher
    ..We also show that IL-1 triggers the interaction of K63-pUb-IRAK1 with NEMO, a regulatory subunit of the IkappaBalpha kinase (IKK) complex, but not with the NEMO[D311N] mutant that cannot ..
  3. Tang E, Wang C, Xiong Y, Guan K. A role for NF-kappaB essential modifier/IkappaB kinase-gamma (NEMO/IKKgamma) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor-alpha. J Biol Chem. 2003;278:37297-305 pubmed
    NEMO (NF-kappaB essential modifier)/IKKgamma (IkappaB kinase-gamma) is required for the activation of the IkappaB kinase complex (IKK) by inflammatory stimuli such as tumor necrosis factor (TNF-alpha)...
  4. Komander D, Reyes Turcu F, Licchesi J, Odenwaelder P, Wilkinson K, Barford D. Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep. 2009;10:466-73 pubmed publisher
    ..We found that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO (NF-kappaB essential modifier) binds to linear chains exclusively, whereas the NZF (Npl4 zinc finger)..
  5. Oeckinghaus A, Wegener E, Welteke V, Ferch U, Arslan S, Ruland J, et al. Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J. 2007;26:4634-45 pubmed
    ..Ubiquitin chains on Malt1 provide a docking surface for the recruitment of the IKK regulatory subunit NEMO/IKKgamma. TRAF6 associates with Malt1 in response to T-cell activation and can function as an E3 ligase for Malt1 in vitro ..
  6. Zhao T, Yang L, Sun Q, Arguello M, Ballard D, Hiscott J, et al. The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways. Nat Immunol. 2007;8:592-600 pubmed
    ..Here we demonstrate that virus-induced activation of IRF3 and IRF7 depended on the NF-kappaB modulator NEMO, which acted 'upstream' of the kinases TBK1 and IKKepsilon...
  7. Lamothe B, Besse A, Campos A, Webster W, Wu H, Darnay B. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. J Biol Chem. 2007;282:4102-12 pubmed
    ..Additionally, we provide biochemical and in vivo evidence that TRAF6 serves as an E3 to directly ubiquitinate NEMO. Reconstituting TRAF6-deficent cells with various TRAF6 mutants, we clearly demonstrate the requirement for the ..
  8. Huang J, Kondo H, Uchio E. A case of incontinentia pigmenti in Japan and its genetic examination. Jpn J Ophthalmol. 2007;51:142-5 pubmed
    b>Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis with approximately one-third of cases with associated ocular complications...
  9. Legarda Addison D, Hase H, O Donnell M, Ting A. NEMO/IKKgamma regulates an early NF-kappaB-independent cell-death checkpoint during TNF signaling. Cell Death Differ. 2009;16:1279-88 pubmed publisher
    ..NF-kappaB essential modifier (NEMO)/IkappaB kinase-gamma (IKKgamma)-deficient cells are highly sensitive to apoptosis, and as NEMO is essential for NF-kappaB activation, it has ..
  10. Hai T, Yeung M, Wood T, Wei Y, Yamaoka S, Gatalica Z, et al. An alternative splice product of IkappaB kinase (IKKgamma), IKKgamma-delta, differentially mediates cytokine and human T-cell leukemia virus type 1 tax-induced NF-kappaB activation. J Virol. 2006;80:4227-41 pubmed
    ..The core IKK consists of two catalytic serine kinases, IKKalpha and IKKbeta, and a noncatalytic subunit, IKKgamma. IKKgamma is required for IKK activity by mediating kinase oligomerization and serving to couple the core ..
  11. Agou F, Ye F, Goffinont S, Courtois G, Yamaoka S, Israel A, et al. NEMO trimerizes through its coiled-coil C-terminal domain. J Biol Chem. 2002;277:17464-75 pubmed
    b>NEMO/IkappaB kinase (IKK) gamma is the regulatory component of the IKK complex comprising the two protein kinases, IKKalpha and IKKbeta...
  12. Verhelst K, Carpentier I, Kreike M, Meloni L, Verstrepen L, Kensche T, et al. A20 inhibits LUBAC-mediated NF-?B activation by binding linear polyubiquitin chains via its zinc finger 7. EMBO J. 2012;31:3845-55 pubmed publisher
    ..Here, we show that A20 is rapidly recruited to NEMO and LUBAC upon TNF stimulation and that A20 inhibits LUBAC-induced NF-?B activation via its C-terminal zinc-finger ..
  13. Tada H, Yoshida S, Yamaji Y, Fujisawa K, Ishibashi T. NEMO mutational analysis in a Japanese family with incontinentia pigmenti. Eye (Lond). 2007;21:888-90 pubmed
  14. Mabb A, Wuerzberger Davis S, Miyamoto S. PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress. Nat Cell Biol. 2006;8:986-93 pubmed
    ..SUMO-1 modification of NEMO (NF-kappaB essential modulator), the IkappaB kinase (IKK) regulatory subunit, is critical for activation of NF-..
  15. Lo Y, Lin S, Rospigliosi C, Conze D, Wu C, Ashwell J, et al. Structural basis for recognition of diubiquitins by NEMO. Mol Cell. 2009;33:602-15 pubmed publisher
    b>NEMO is the regulatory subunit of the IkappaB kinase (IKK) in NF-kappaB activation, and its CC2-LZ region interacts with Lys63 (K63)-linked polyubiquitin to recruit IKK to receptor signaling complexes...
  16. Wang Y, Li L, Han K, Zhai Z, Shu H. A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF-kappaB and ISRE and IFN-beta promoter. FEBS Lett. 2004;576:86-90 pubmed
    ..These data suggest that A20 targets TRIF to inhibit TLR3-mediated induction of IFN-beta transcription and functions as a feedback negative regulator for TLR3 signaling and cellular anti-viral response. ..
  17. Kovalenko A, Chable Bessia C, Cantarella G, Israel A, Wallach D, Courtois G. The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature. 2003;424:801-5 pubmed
    ..Here we report that CYLD, a tumour suppressor that is mutated in familial cylindromatosis, interacts with NEMO, the regulatory subunit of IKK...
  18. Strnad J, McDonnell P, Riexinger D, Mapelli C, Cheng L, Gray H, et al. NEMO binding domain of IKK-2 encompasses amino acids 735-745. J Mol Recognit. 2006;19:227-33 pubmed
    ..Though this signalsome is comprised of IKK-1, IKK-2, and NEMO/IKKgamma, it is the interaction between IKK-2 and NEMO that is critical to formation of a functional signalsome...
  19. May M, Marienfeld R, Ghosh S. Characterization of the Ikappa B-kinase NEMO binding domain. J Biol Chem. 2002;277:45992-6000 pubmed
    ..IKK) composed of two catalytic subunits (IKKalpha and IKKbeta) and a noncatalytic regulatory component named NEMO (NF-kappaB essential modulator)...
  20. Jin D, Giordano V, Kibler K, Nakano H, Jeang K. 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. J Biol Chem. 1999;274:17402-5 pubmed
    ..Thus, our findings establish IKK-gamma as a key molecule for adapting an oncoprotein-specific signaling to IKK-alpha and IKK-beta. ..
  21. Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, et al. Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-?B regulation. EMBO J. 2012;31:3856-70 pubmed publisher
    ..ubiquitin chain assembly complex) activates the canonical NF-?B pathway through linear polyubiquitination of NEMO (NF-?B essential modulator, also known as IKK?) and RIP1...
  22. Conze D, Wu C, Thomas J, Landstrom A, Ashwell J. Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation. Mol Cell Biol. 2008;28:3538-47 pubmed publisher
    ..and IRAK-1 acquired Lys63 (K63)-linked polyubiquitin chains upon IL-1 stimulation, only ubiquitinated IRAK-1 bound NEMO, the regulatory subunit of IkappaB kinase (IKK)...
  23. Higashimoto T, Chan N, Lee Y, Zandi E. Regulation of I(kappa)B kinase complex by phosphorylation of (gamma)-binding domain of I(kappa)B kinase (beta) by Polo-like kinase 1. J Biol Chem. 2008;283:35354-67 pubmed publisher
    IkappaB kinase (IKK) complex is a key regulator of NF-kappaB pathways. Signal-induced interaction of the IKKgamma (NEMO) subunit with the C-terminal IKKgamma/NEMO-binding domain (gammaBD) of IKKbeta is an essential interaction for IKK ..
  24. Chaudhary P, Eby M, Jasmin A, Kumar A, Liu L, Hood L. Activation of the NF-kappaB pathway by caspase 8 and its homologs. Oncogene. 2000;19:4451-60 pubmed
    ..Thus, DEDs-containing caspases and caspase homolog(s) may have functions beyond their known role in the mediation of cell death. Oncogene (2000) 19, 4451 - 4460. ..
  25. Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, Sakata S, et al. SHARPIN is a component of the NF-?B-activating linear ubiquitin chain assembly complex. Nature. 2011;471:633-6 pubmed publisher
    ..with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-?B essential modulator; also known as IKBKG)...
  26. Hinz M, Stilmann M, Arslan S, Khanna K, Dittmar G, Scheidereit C. A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-?B activation. Mol Cell. 2010;40:63-74 pubmed publisher
    ..Our data indicate that exported SUMOylated IKK? acts as a substrate. IKK? monoubiquitination is a prerequisite for genotoxic IKK and NF-?B activation, but also promotes cytokine signaling. ..
  27. Fusco F, Pescatore A, Bal E, Ghoul A, Paciolla M, Lioi M, et al. Alterations of the IKBKG locus and diseases: an update and a report of 13 novel mutations. Hum Mutat. 2008;29:595-604 pubmed publisher
    ..called nuclear factor-kappaB (NF-kB) essential modulator (NEMO), gene are the most common single cause of incontinentia pigmenti (IP) in females and anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males...
  28. Poyet J, Srinivasula S, Lin J, Fernandes Alnemri T, Yamaoka S, Tsichlis P, et al. Activation of the Ikappa B kinases by RIP via IKKgamma /NEMO-mediated oligomerization. J Biol Chem. 2000;275:37966-77 pubmed
    ..Substitution of the C-terminal region of IKKgamma, which interacts with RIP, with a truncated DR4 lacking its cytoplasmic death domain, produced a molecule that ..
  29. Marienfeld R, Palkowitsch L, Ghosh S. Dimerization of the I kappa B kinase-binding domain of NEMO is required for tumor necrosis factor alpha-induced NF-kappa B activity. Mol Cell Biol. 2006;26:9209-19 pubmed
    Previous studies have demonstrated that peptides corresponding to a six-amino-acid NEMO-binding domain from the C terminus of IkappaB kinase alpha (IKKalpha) and IKKbeta can disrupt the IKK complex and block NF-kappaB activation...
  30. Zotti T, Uva A, Ferravante A, Vessichelli M, Scudiero I, Ceccarelli M, et al. TRAF7 protein promotes Lys-29-linked polyubiquitination of IkappaB kinase (IKKgamma)/NF-kappaB essential modulator (NEMO) and p65/RelA protein and represses NF-kappaB activation. J Biol Chem. 2011;286:22924-33 pubmed publisher
    ..the unique noncanonical member of the TRAF family, physically associates with I?B kinase/NF-?B essential modulator (NEMO) and with the RelA/p65 (p65) member of the NF-?B transcription factor family...
  31. Conte M, Pescatore A, Paciolla M, Esposito E, Miano M, Lioi M, et al. Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to incontinentia pigmenti disease. Hum Mutat. 2014;35:165-77 pubmed publisher
    b>Incontinentia pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of nuclear factor kappaB (NF-kB) signaling...
  32. Deng L, Wang C, Spencer E, Yang L, Braun A, You J, et al. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000;103:351-61 pubmed
    ..These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains. ..
  33. Rothwarf D, Zandi E, Natoli G, Karin M. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature. 1998;395:297-300 pubmed
    ..IKK-gamma interacts preferentially with IKK-beta and is required for the activation of the IKK complex. An IKK-gamma carboxy-terminal truncation mutant that still binds IKK-beta blocks the activation of IKK and NF-kappaB. ..
  34. O Donnell M, Hase H, Legarda D, Ting A. NEMO inhibits programmed necrosis in an NF?B-independent manner by restraining RIP1. PLoS ONE. 2012;7:e41238 pubmed publisher
    ..We demonstrate that T cells lacking the regulatory subunit of IKK, NF?B essential modifier (NEMO), are hypersensitive to programmed necrosis when stimulated with TNF in the presence of caspase inhibitors...
  35. Pertel T, Hausmann S, Morger D, Z├╝ger S, Guerra J, Lascano J, et al. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011;472:361-5 pubmed publisher
  36. Xia Z, Sun L, Chen X, Pineda G, Jiang X, Adhikari A, et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature. 2009;461:114-9 pubmed publisher
    ..These results indicate that unanchored polyubiquitin chains directly activate TAK1 and IKK, suggesting a new mechanism of protein kinase regulation. ..
  37. Wagner S, Carpentier I, Rogov V, Kreike M, Ikeda F, Lohr F, et al. Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins. Oncogene. 2008;27:3739-45 pubmed publisher
    ..Moreover, this region is also present in NF-kappaB essential modulator/IkappaB kinase gamma (NEMO/IKKgamma) and the NEMO-like protein optineurin, and is therefore termed UBD in ABIN proteins and NEMO (UBAN)...
  38. Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U. Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. J Biol Chem. 2002;277:37029-36 pubmed
    ..alpha and IKK beta subunits and a presumed regulatory protein termed NEMO (NF-kappa B essential modulator) or IKK gamma. NEMO/IKK gamma is indispensable for activation of the IKKs in response to many signals, but its mechanism of ..
  39. Ordureau A, Smith H, Windheim M, Peggie M, Carrick E, Morrice N, et al. The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1. Biochem J. 2008;409:43-52 pubmed
    ..2, but not inactive mutants of these proteins, induces the formation of K63-pUb-IRAK1 and its interaction with the NEMO [NF-kappaB (nuclear factor kappaB) essential modifier] regulatory subunit of the IKK (inhibitor of NF-kappaB kinase)..
  40. Prajapati S, Verma U, Yamamoto Y, Kwak Y, Gaynor R. Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity. J Biol Chem. 2004;279:1739-46 pubmed
    ..These studies are consistent with the ability of PP2Cbeta to down-regulate cytokine-induced NF-kappaB activation by altering IKK activity. ..
  41. Wu Z, Shi Y, Tibbetts R, Miyamoto S. Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science. 2006;311:1141-6 pubmed
    ..We show that NF-kappaB essential modulator (NEMO), the regulatory subunit of IkappaB kinase (IKK) (which phosphorylates the NF-kappaB inhibitor IkappaB), associates ..
  42. Makris C, Roberts J, Karin M. The carboxyl-terminal region of IkappaB kinase gamma (IKKgamma) is required for full IKK activation. Mol Cell Biol. 2002;22:6573-81 pubmed
    ..IKKgamma is encoded by an X-linked gene, deficiencies in which may result in two human genetic disorders, incontinentia pigmenti (IP) and hypohidrotic ectodermal dysplasia with severe immunodeficiency...
  43. Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell. 2009;136:1098-109 pubmed publisher
    ..a key mediator of inducible transcription in immunity, requires binding of NF-kappaB essential modulator (NEMO) to ubiquitinated substrates...
  44. Solt L, Madge L, Orange J, May M. Interleukin-1-induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta. J Biol Chem. 2007;282:8724-33 pubmed
    ..kinase (IKK) complex, which contains two kinases named IKKalpha and IKKbeta and a critical regulatory subunit named NEMO. Although we have previously demonstrated that NEMO associates with both IKKs, genetic studies reveal that only its ..
  45. Brummelkamp T, Nijman S, Dirac A, Bernards R. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature. 2003;424:797-801 pubmed
    ..We show that CYLD binds to the NEMO (also known as IKKgamma) component of the IkappaB kinase (IKK) complex, and appears to regulate its activity through de-ubiquitination of ..
  46. Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature. 2000;405:466-72 pubmed
    Familial incontinentia pigmenti (IP; MIM 308310) is a genodermatosis that segregates as an X-linked dominant disorder and is usually lethal prenatally in males...
  47. Carter R, Pennington K, Ungurait B, Ballard D. In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase. J Biol Chem. 2003;278:19642-8 pubmed
    ..two structurally related catalytic subunits termed IKKalpha and IKKbeta as well as a noncatalytic subunit called IKKgamma/NEMO...
  48. Xiao G, Sun S. Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein. Oncogene. 2000;19:5198-203 pubmed
    ..Tax activation of IKK requires physical interaction of this viral protein with the IKK regulatory subunit, IKKgamma. The Tax/IKKgamma interaction allows Tax to engage the IKK catalytic subunits, IKKalpha and IKKbeta, although it ..
  49. Laplantine E, Fontan E, Chiaravalli J, Lopez T, Lakisic G, Veron M, et al. NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain. EMBO J. 2009;28:2885-95 pubmed publisher
    An important property of NEMO, the core element of the IKK complex involved in NF-kappaB activation, resides in its ability to specifically recognize poly-ubiquitin chains...
  50. Daubeuf S, Singh D, Tan Y, Liu H, Federoff H, Bowers W, et al. HSV ICP0 recruits USP7 to modulate TLR-mediated innate response. Blood. 2009;113:3264-75 pubmed publisher
    ..Cytoplasmic USP7 binds to and deubiquitinates TRAF6 and IKKgamma, thus terminating TLR-mediated NF-kappaB and JNK activation...
  51. Li H, Kobayashi M, Blonska M, You Y, Lin X. Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J Biol Chem. 2006;281:13636-43 pubmed
    ..Together, our studies provide the first genetic evidence that the ubiquitination of RIP is required for TNFalpha-induced NF-kappaB activation. ..
  52. Tegethoff S, Behlke J, Scheidereit C. Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation. Mol Cell Biol. 2003;23:2029-41 pubmed
    ..Its catalytic subunits, IKKalpha and IKKbeta, require association with the regulatory IKKgamma (NEMO) component to gain full basal and inducible kinase activity...
  53. Ea C, Deng L, Xia Z, Pineda G, Chen Z. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006;22:245-57 pubmed
    ..Interestingly, polyubiquitinated RIP1 recruits IKK through the binding between the polyubiquitin chains and NEMO, a regulatory subunit of the IKK complex...
  54. Inohara N, Koseki T, Lin J, del Peso L, Lucas P, Chen F, et al. An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways. J Biol Chem. 2000;275:27823-31 pubmed
    ..of Nod1 mediates proximity of RICK and the interaction of RICK with the gamma subunit of the IkappaB kinase (IKKgamma). Similarly, the RICK-related kinase RIP associated via its intermediate region with IKKgamma...
  55. Reiley W, Zhang M, Wu X, Granger E, Sun S. Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent phosphorylation. Mol Cell Biol. 2005;25:3886-95 pubmed
    ..Interestingly, the CYLD phosphorylation requires IkappaB kinase gamma (IKKgamma) and can be induced by IKK catalytic subunits...
  56. Cordier F, Vinolo E, Veron M, Delepierre M, Agou F. Solution structure of NEMO zinc finger and impact of an anhidrotic ectodermal dysplasia with immunodeficiency-related point mutation. J Mol Biol. 2008;377:1419-32 pubmed publisher
    The regulatory NEMO (NF-kappaB essential modulator) protein has a crucial role in the canonical NF-kappaB signaling pathway notably involved in immune and inflammatory responses, apoptosis and oncogenesis...
  57. Hsiao P, Lin S, Chiang S, Wu Y, Chen H, Lin Y. NEMO gene mutations in Chinese patients with incontinentia pigmenti. J Formos Med Assoc. 2010;109:192-200 pubmed publisher
    b>Incontinentia pigmenti is a rare, X-linked, dominant genodermatosis affecting skin, teeth, eyes, and central nervous system...
  58. Bloor S, Ryzhakov G, Wagner S, Butler P, Smith D, Krumbach R, et al. Signal processing by its coil zipper domain activates IKK gamma. Proc Natl Acad Sci U S A. 2008;105:1279-84 pubmed publisher
    ..Activity of IKK is governed by its noncatalytic subunit IKKgamma. Signaling defects due to missense mutations in IKKgamma have been correlated to its inability to either become ..
  59. Song M, Chae J, Park E, Ki C. The common NF-?B essential modulator (NEMO) gene rearrangement in Korean patients with incontinentia pigmenti. J Korean Med Sci. 2010;25:1513-7 pubmed publisher
    b>Incontinentia pigmenti (IP) is a rare X-linked dominant disorder characterized by highly variable abnormalities of the skin, eyes and central nervous system...
  60. Dong W, Liu Y, Peng J, Chen L, Zou T, Xiao H, et al. The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4. J Biol Chem. 2006;281:26029-40 pubmed
    ..We show that BCL10 oligomerization is a prerequisite for BCL10 function in LPS signaling to NF-kappaB and that IRAK-1 dimerization is an important event in this process. ..
  61. Hadian K, Griesbach R, Dornauer S, Wanger T, Nagel D, Metlitzky M, et al. NF-?B essential modulator (NEMO) interaction with linear and lys-63 ubiquitin chains contributes to NF-?B activation. J Biol Chem. 2011;286:26107-17 pubmed publisher
    ..IKK activation requires sensing of ubiquitin chains by the essential IKK regulatory subunit IKK?/NEMO. However, it has remained enigmatic whether NEMO binding to Lys-63-linked or linear ubiquitin chains is critical ..
  62. Damgaard R, Nachbur U, Yabal M, Wong W, Fiil B, Kastirr M, et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012;46:746-58 pubmed publisher
    ..We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis. ..
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