Ikbkg

Summary

Gene Symbol: Ikbkg
Description: inhibitor of kappaB kinase gamma
Alias: 1110037D23Rik, AI848108, AI851264, AW124339, IKK[g], NEMO, NF-kappa-B essential modulator, I-kappa-B kinase subunit gamma, IKK-gamma, IKKAP1, IKKG, NF-kappa-B essential modifier, ikB kinase subunit gamma, ikB kinase-associated protein 1, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma, inhibitor of nuclear factor kappa-B kinase subunit gamma, mFIP-3
Species: mouse
Products:     Ikbkg

Top Publications

  1. Liedtke C, Bangen J, Freimuth J, Beraza N, Lambertz D, Cubero F, et al. Loss of caspase-8 protects mice against inflammation-related hepatocarcinogenesis but induces non-apoptotic liver injury. Gastroenterology. 2011;141:2176-87 pubmed publisher
    Disruption of the nuclear factor-?B (NF-?B) essential modulator (NEMO) in hepatocytes of mice (NEMO(?hepa) mice) results in spontaneous liver apoptosis and chronic liver disease involving inflammation, steatosis, fibrosis, and development ..
  2. Saijo K, Mecklenbrauker I, Santana A, Leitger M, Schmedt C, Tarakhovsky A. Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha. J Exp Med. 2002;195:1647-52 pubmed
  3. Luedde T, Heinrichsdorff J, De Lorenzi R, De Vos R, Roskams T, Pasparakis M. IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver. Proc Natl Acad Sci U S A. 2008;105:9733-8 pubmed publisher
    ..Unexpectedly, mice with combined ablation of IKK1 and IKK2 or IKK1 and NEMO spontaneously developed severe jaundice and fatal cholangitis characterized by inflammatory destruction of small ..
  4. Verma I, Stevenson J, Schwarz E, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35 pubmed
  5. 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...
  6. Hacker H, Redecke V, Blagoev B, Kratchmarova I, Hsu L, Wang G, et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature. 2006;439:204-7 pubmed
  7. Luedde T, Beraza N, Kotsikoris V, Van Loo G, Nenci A, De Vos R, et al. Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell. 2007;11:119-32 pubmed
    The IkappaB kinase (IKK) subunit NEMO/IKKgamma is essential for activation of the transcription factor NF-kappaB, which regulates cellular responses to inflammation. The function of NEMO in the adult liver remains elusive...
  8. Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, et al. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol. 2009;11:123-32 pubmed publisher
    ..Here, we demonstrate that LUBAC activates the canonical NF-kappaB pathway by binding to NEMO (NF-kappaB essential modulator, also called IKKgamma) and conjugates linear polyubiquitin chains onto specific Lys ..
  9. Rudolph D, Yeh W, Wakeham A, Rudolph B, Nallainathan D, Potter J, et al. Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice. Genes Dev. 2000;14:854-62 pubmed
    ..A novel, noncatalytic component of this kinase complex called NEMO (NF-kappaB essential modulator)/IKKgamma was identified recently...

More Information

Publications91

  1. Irrinki K, Mallilankaraman K, Thapa R, Chandramoorthy H, Smith F, Jog N, et al. Requirement of FADD, NEMO, and BAX/BAK for aberrant mitochondrial function in tumor necrosis factor alpha-induced necrosis. Mol Cell Biol. 2011;31:3745-58 pubmed publisher
    ..Here, we show that tumor necrosis factor alpha (TNF-?)-induced necroptosis requires the adaptor proteins FADD and NEMO. FADD was found to mediate formation of the TNF-?-induced pronecrotic RIP1-RIP3 kinase complex, whereas the I?B ..
  2. Gautheron J, Pescatore A, Fusco F, Esposito E, Yamaoka S, Agou F, et al. Identification of a new NEMO/TRAF6 interface affected in incontinentia pigmenti pathology. Hum Mol Genet. 2010;19:3138-49 pubmed publisher
    NF-kappaB Essential MOdulator (NEMO) has been shown to play a critical role in NF-kappaB activation, as the regulatory subunit of IkappaB kinase...
  3. Wright A, Reiley W, Chang M, Jin W, Lee A, Zhang M, et al. Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD. Dev Cell. 2007;13:705-16 pubmed
    ..These findings establish CYLD as a pivotal deubiquitinating enzyme (DUB) that regulates germ cell apoptosis and spermatogenesis and suggest an essential role for CYLD in controlling the RIP1/NF-kappaB signaling axis in testis. ..
  4. 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...
  5. Cubero F, Singh A, Borkham Kamphorst E, Nevzorova Y, Al Masaoudi M, Haas U, et al. TNFR1 determines progression of chronic liver injury in the IKK?/Nemo genetic model. Cell Death Differ. 2013;20:1580-92 pubmed publisher
    ..Deletion of NF-?B essential modulator in hepatocytes (IKK?/Nemo) causes spontaneous progression of TNF-mediated chronic hepatitis to hepatocellular carcinoma (HCC)...
  6. Wang L, Li S, Dorf M. NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses. PLoS ONE. 2012;7:e43756 pubmed publisher
    ..Ubiquitinated TBK1 recruits the downstream adaptor NEMO through ubiquitin binding domains...
  7. 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...
  8. Beraza N, Ludde T, Assmus U, Roskams T, Vander Borght S, Trautwein C. Hepatocyte-specific IKK gamma/NEMO expression determines the degree of liver injury. Gastroenterology. 2007;132:2504-17 pubmed
    b>NEMO is the regulatory subunit of the I kappa B kinase (IKK) complex and is involved in controlling nuclear factor kappaB (NF-kappaB) activation. NEMO knockout mice die during embryogenesis due to massive hepatocyte apoptosis...
  9. 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 ..
  10. Nenci A, Becker C, Wullaert A, Gareus R, Van Loo G, Danese S, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature. 2007;446:557-61 pubmed
    ..Intestinal epithelial-cell-specific inhibition of NF-kappaB through conditional ablation of NEMO (also called IkappaB kinase-gamma (IKKgamma)) or both IKK1 (IKKalpha) and IKK2 (IKKbeta)-IKK subunits essential for ..
  11. Schmidt Supprian M, Bloch W, Courtois G, Addicks K, Israel A, Rajewsky K, et al. NEMO/IKK gamma-deficient mice model incontinentia pigmenti. Mol Cell. 2000;5:981-92 pubmed
    Disruption of the X-linked gene encoding NF-kappa B essential modulator (NEMO) produces male embryonic lethality, completely blocks NF-kappa B activation by proinflammatory cytokines, and interferes with the generation and/or persistence ..
  12. 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...
  13. Beraza N, Malato Y, Sander L, Al Masaoudi M, Freimuth J, Riethmacher D, et al. Hepatocyte-specific NEMO deletion promotes NK/NKT cell- and TRAIL-dependent liver damage. J Exp Med. 2009;206:1727-37 pubmed publisher
    ..The IKK complex mediates NF-kappaB activation and deletion of its regulatory subunit NEMO in hepatocytes (NEMO(Delta hepa)) triggers chronic inflammation and spontaneous hepatocellular carcinoma ..
  14. 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)...
  15. Yamaoka S, Courtois G, Bessia C, Whiteside S, Weil R, Agou F, et al. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Cell. 1998;93:1231-40 pubmed
    ..The recovered full-length cDNA encodes a 48 kDa protein, NEMO (NF-kappaB Essential MOdulator), which contains a putative leucine zipper motif...
  16. 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
    ..IKK has two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, IKKgamma or NEMO. NEMO is essential for NF-kappaB activation, and NEMO dysfunction in humans is the cause of incontinentia pigmenti ..
  17. O Donnell M, Perez Jimenez E, Oberst A, Ng A, Massoumi R, Xavier R, et al. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat Cell Biol. 2011;13:1437-42 pubmed publisher
    ..In contrast, loss of caspase 8 prevented CYLD degradation, resulting in necrotic death. A CYLD substitution mutation at Asp 215 that cannot be cleaved by caspase 8 switches cell survival to necrotic cell death in response to TNF. ..
  18. Sasaki Y, Derudder E, Hobeika E, Pelanda R, Reth M, Rajewsky K, et al. Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation. Immunity. 2006;24:729-39 pubmed
    ..Inhibition of canonical NF-kappaB transcription factor activity through ablation of the essential scaffold protein NEMO arrests B cell development at the same stage as BAFF-R deficiency...
  19. Makris C, Godfrey V, Krähn Senftleben G, Takahashi T, Roberts J, Schwarz T, et al. Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti. Mol Cell. 2000;5:969-79 pubmed
    b>IKK gamma/NEMO is the essential regulatory subunit of the I kappa B kinase (IKK), encoded by an X-linked gene in mice and humans. It is required for NF-kappa B activation and resistance to TNF-induced apoptosis...
  20. Pasparakis M, Schmidt Supprian M, Rajewsky K. IkappaB kinase signaling is essential for maintenance of mature B cells. J Exp Med. 2002;196:743-52 pubmed
    ..which is composed of two kinases, IKK1 and IKK2, and a regulatory subunit termed NF-kappaB essential modulator (NEMO). IKK2- and NEMO-deficient mice die at early embryonic stages...
  21. Derudder E, Herzog S, Labi V, Yasuda T, Köchert K, Janz M, et al. Canonical NF-?B signaling is uniquely required for the long-term persistence of functional mature B cells. Proc Natl Acad Sci U S A. 2016;113:5065-70 pubmed publisher
    ..To resolve this conflict, we ablated NF-?B essential modulator (NEMO) and I?B kinase 2 (IKK2), two essential mediators of the canonical pathway, either early on in B-cell development ..
  22. Espinosa L, Cathelin S, D Altri T, Trimarchi T, Statnikov A, Guiu J, et al. The Notch/Hes1 pathway sustains NF-?B activation through CYLD repression in T cell leukemia. Cancer Cell. 2010;18:268-81 pubmed publisher
  23. Kratsios P, Huth M, Temmerman L, Salimova E, Al Banchaabouchi M, Sgoifo A, et al. Antioxidant amelioration of dilated cardiomyopathy caused by conditional deletion of NEMO/IKKgamma in cardiomyocytes. Circ Res. 2010;106:133-44 pubmed publisher
    ..pathway specifically in mouse cardiomyocytes by conditional deletion of the NF-kappaB essential modulator (NEMO)...
  24. Xing J, Weng L, Yuan B, Wang Z, Jia L, Jin R, et al. Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract. Nat Immunol. 2016;17:1373-1380 pubmed publisher
    ..interferon-regulatory factors and signaling via the transcription factor NF-κB by degrading the adaptor NEMO and that TRIM29 directly bound NEMO and subsequently induced its ubiquitination and proteolytic degradation...
  25. Pescatore A, Esposito E, Dráber P, Walczak H, Ursini M. NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II. Cell Death Dis. 2016;7:e2346 pubmed publisher
    ..IP is caused by NF-κB essential modulator (NEMO) mutations...
  26. Shinohara H, Yasuda T, Aiba Y, Sanjo H, Hamadate M, Watarai H, et al. PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1. J Exp Med. 2005;202:1423-31 pubmed
    ..Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCbeta, brings two key protein kinases, TAK1 and IKK, into close proximity, thereby allowing TAK1 to phosphorylate IKK. ..
  27. Krause E, de Graaf M, Fliss P, Dölken L, Brune W. Murine cytomegalovirus virion-associated protein M45 mediates rapid NF-?B activation after infection. J Virol. 2014;88:9963-75 pubmed publisher
    ..gamma subunit of the inhibitor of ?B kinase complex (IKK?; commonly referred to as the NF-?B essential modulator [NEMO]). Here we show that the viral M45 protein also mediates rapid NF-?B activation immediately after infection...
  28. Besse A, Lamothe B, Campos A, Webster W, Maddineni U, Lin S, et al. TAK1-dependent signaling requires functional interaction with TAB2/TAB3. J Biol Chem. 2007;282:3918-28 pubmed
    ..Significantly, our study provides evidence that the TAB2/TAB3 interaction with TAK1 is crucial for the activation of signaling cascades mediated by IL-1, TNF, and RANKL. ..
  29. Panda S, Nilsson J, Gekara N. Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes. Immunity. 2015;43:647-59 pubmed publisher
    ..This study identifies MYSM1 as a key negative regulator of the innate immune system that guards against an overzealous self-destructive immune response. ..
  30. Bettermann K, Vucur M, Haybaeck J, Koppe C, Janssen J, Heymann F, et al. TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer. Cancer Cell. 2010;17:481-96 pubmed publisher
    ..depends on NF-kappaB-independent functions of the I kappaB-kinase (IKK)-subunit NF-kappaB essential modulator (NEMO)...
  31. Kim H, Kim J, Moon M, Park S, Park J. I?B kinase ?/nuclear factor-?B-essential modulator (IKK?/NEMO) facilitates RhoA GTPase activation, which, in turn, activates Rho-associated KINASE (ROCK) to phosphorylate IKK? in response to transforming growth factor (TGF)-?1. J Biol Chem. 2014;289:1429-40 pubmed publisher
  32. Tseng P, Matsuzawa A, Zhang W, Mino T, Vignali D, Karin M. Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines. Nat Immunol. 2010;11:70-5 pubmed publisher
    ..Inhibition of degradative ubiquitination of TRAF3 prevented the expression of all proinflammatory cytokines without affecting the interferon response. ..
  33. Agou F, Courtois G, Chiaravalli J, Baleux F, Coic Y, Traincard F, et al. Inhibition of NF-kappa B activation by peptides targeting NF-kappa B essential modulator (nemo) oligomerization. J Biol Chem. 2004;279:54248-57 pubmed
    NF-kappa B essential modulator/IKK-gamma (NEMO/IKK-gamma) plays a key role in the activation of the NF-kappa B pathway in response to proinflammatory stimuli...
  34. Fliss P, Jowers T, Brinkmann M, Holstermann B, Mack C, Dickinson P, et al. Viral mediated redirection of NEMO/IKK? to autophagosomes curtails the inflammatory cascade. PLoS Pathog. 2012;8:e1002517 pubmed publisher
    ..Inhibition occurs through an interaction of the viral M45 protein with the NF-?B essential modulator (NEMO), the regulatory subunit of the IKK complex...
  35. Farhana L, Dawson M, Murshed F, Fontana J. Maximal adamantyl-substituted retinoid-related molecule-induced apoptosis requires NF-?B noncanonical and canonical pathway activation. Cell Death Differ. 2011;18:164-73 pubmed publisher
    ..Cdc37 expression was required for activation of IKK? and IKK? by 3-Cl-AHPC. These findings suggest that NF-?B pathways have an important role in 3-Cl-AHPC-mediated apoptosis. ..
  36. Fujita H, Rahighi S, Akita M, Kato R, Sasaki Y, Wakatsuki S, et al. Mechanism underlying I?B kinase activation mediated by the linear ubiquitin chain assembly complex. Mol Cell Biol. 2014;34:1322-35 pubmed publisher
    ..LUBAC-mediated linear polyubiquitination has been implicated in NF-?B activation. NEMO, a component of the I?B kinase (IKK) complex, is a substrate of LUBAC, but the precise molecular mechanism ..
  37. Ikeda F, Deribe Y, Skånland S, Stieglitz B, Grabbe C, Franz Wachtel M, et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-?B activity and apoptosis. Nature. 2011;471:637-41 pubmed publisher
    ..Coexpression of SHARPIN and HOIP promotes linear ubiquitination of NEMO (also known as IKBKG), an adaptor of the I?B kinases (IKKs) and subsequent activation of NF-?B signalling, whereas SHARPIN deficiency ..
  38. Prajapati S, Gaynor R. Regulation of Ikappa B kinase (IKK)gamma /NEMO function by IKKbeta -mediated phosphorylation. J Biol Chem. 2002;277:24331-9 pubmed
    ..IKK) complex includes the catalytic components IKKalpha and IKKbeta in addition to the scaffold protein IKKgamma/NEMO. Increases in the activity of the IKK complex result in the phosphorylation and subsequent degradation of IkappaB ..
  39. Torres J, Watt F. Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NFkappaB and cooperating with Stat3. Nat Cell Biol. 2008;10:194-201 pubmed publisher
    ..proteins promoted differentiation, whereas inhibition of NFkappaB signalling, either by genetic ablation of the Ikbkg gene or overexpression of the IkappaBalpha super-repressor, increased expression of pluripotency markers...
  40. Zhao Y, Ma C, Wu L, Iwai K, Ashwell J, Oltz E, et al. CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early Embryogenesis. J Biol Chem. 2015;290:22076-84 pubmed publisher
    NF-κB essential modulator (NEMO) and cylindromatosis protein (CYLD) are intracellular proteins that regulate the NF-κB signaling pathway...
  41. Yamamoto M, Sato S, Saitoh T, Sakurai H, Uematsu S, Kawai T, et al. Cutting Edge: Pivotal function of Ubc13 in thymocyte TCR signaling. J Immunol. 2006;177:7520-4 pubmed
    ..In addition, PMA/ionophore-mediated ubiquitination of NF-kappaB essential modulator (NEMO)/IkappaB kinase gamma (IKKgamma) and phosphorylation of TGF-beta-activated kinase 1 (TAK1) were nearly abolished in ..
  42. Kim S, La Motte Mohs R, Rudolph D, Zuniga Pflucker J, Mak T. The role of nuclear factor-kappaB essential modulator (NEMO) in B cell development and survival. Proc Natl Acad Sci U S A. 2003;100:1203-8 pubmed
    ..NF-kappaB essential modulator (NEMO) is a scaffolding component of the IkappaB kinase complex required for NF-kappaB activation in vitro...
  43. Stilmann M, Hinz M, Arslan S, Zimmer A, Schreiber V, Scheidereit C. A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation. Mol Cell. 2009;36:365-78 pubmed publisher
    ..kinase ataxia talengiectasia mutated (ATM) have been implicated to SUMOylate and phosphorylate nuclear IKKgamma (NEMO) in a consecutive mode of action, which in turn results in activation of cytoplasmic IKK holocomplexes...
  44. Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, et al. 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. Proc Natl Acad Sci U S A. 1999;96:1042-7 pubmed
    ..Because the activation of NF-kappaB has been shown to inhibit apoptosis, FIP-3 appears both to activate a cell-death pathway and to inhibit an NF-kappaB-dependent survival mechanism. ..
  45. Jun J, Kertesy S, Jones M, Marinis J, Cobb B, Tigno Aranjuez J, et al. Innate immune-directed NF-?B signaling requires site-specific NEMO ubiquitination. Cell Rep. 2013;4:352-61 pubmed publisher
    While the I kappa kinase (IKK) scaffolding protein NF-?B essential modulator (NEMO) binds to polyubiquitin chains to transmit inflammatory signals, NEMO itself is also ubiquitinated in response to a variety of inflammatory agonists...
  46. Alhawagri M, Yamanaka Y, BALLARD D, Oltz E, Abu Amer Y. Lysine392, a K63-linked ubiquitination site in NEMO, mediates inflammatory osteoclastogenesis and osteolysis. J Orthop Res. 2012;30:554-60 pubmed publisher
    ..The IKK complex consists of IKK?, IKK?, and IKK?, also known as NEMO. NEMO has no catalytic activity and serves as a scaffold protein facilitating assembly and distal activation of NF-?..
  47. Ammirante M, Rosati A, Arra C, Basile A, Falco A, Festa M, et al. IKK{gamma} protein is a target of BAG3 regulatory activity in human tumor growth. Proc Natl Acad Sci U S A. 2010;107:7497-502 pubmed publisher
    ..As a proof of principle, we show that treatment of a mouse xenograft tumor model with bag3siRNA-adenovirus that down-regulates bag3 results in reduced tumor growth and increased animal survival. ..
  48. Chang J, Wang Z, Tang E, Fan Z, McCauley L, Franceschi R, et al. Inhibition of osteoblastic bone formation by nuclear factor-kappaB. Nat Med. 2009;15:682-9 pubmed publisher
    ..Taken together, our results suggest that targeting IKK-NF-kappaB may help to promote bone formation in the treatment of osteoporosis and other bone diseases. ..
  49. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher M. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007;282:36223-9 pubmed
    ..tuberculosis-induced Rip2 polyubiquitination appears MyD88-independent. Collectively, these data reveal that the NOD2 pathway is ubiquitin-regulated and that Rip2 employs a ubiquitin-dependent mechanism to achieve NF-kappaB activation. ..
  50. Song Y, Lee Y, Chan P. Oxidative stress transiently decreases the IKK complex (IKKalpha, beta, and gamma), an upstream component of NF-kappaB signaling, after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 2005;25:1301-11 pubmed
    ..These results suggest that ROS are implicated in transient downregulation of IKKalpha, beta, and gamma in cerebral ischemia. ..
  51. Arimoto K, Funami K, Saeki Y, Tanaka K, Okawa K, Takeuchi O, et al. Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense. Proc Natl Acad Sci U S A. 2010;107:15856-61 pubmed publisher
    ..According to recent studies, the NF-kappaB essential modulator (NEMO, also called IKKgamma) is crucial for this virus-induced antiviral response...
  52. Reale C, Iervolino A, Scudiero I, Ferravante A, D Andrea L, Mazzone P, et al. NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function. J Biol Chem. 2016;291:5765-73 pubmed publisher
    The I-κB kinase (IKK) subunit NEMO/IKKγ (NEMO) is an adapter molecule that is critical for canonical activation of NF-κB, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and ..
  53. Solt L, Madge L, May M. NEMO-binding domains of both IKKalpha and IKKbeta regulate IkappaB kinase complex assembly and classical NF-kappaB activation. J Biol Chem. 2009;284:27596-608 pubmed publisher
    ..two catalytic subunits named IKKalpha and IKKbeta and a regulatory subunit named NF-kappaB essential modulator (NEMO)...
  54. Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U. CIKS, a connection to Ikappa B kinase and stress-activated protein kinase. Proc Natl Acad Sci U S A. 2000;97:10494-9 pubmed
    ..IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma...
  55. Guo L, Lee H, Noriega M, Paust H, Zahner G, Thaiss F. Lymphocyte-specific deletion of IKK2 or NEMO mediates an increase in intrarenal Th17 cells and accelerates renal damage in an ischemia-reperfusion injury mouse model. Am J Physiol Renal Physiol. 2016;311:F1005-F1014 pubmed publisher
    ..Here, we investigated whether deletion of the NF-?B kinases IKK2 or NEMO in lymphocytes or systemic inhibition of IKK2 would cause different kidney inflammatory responses after IRI ..
  56. Saso K, Ito T, Natori S, Sekimizu K. Identification of a novel tissue-specific transcriptional activator FESTA as a protein that interacts with the transcription elongation factor S-II. J Biochem. 2003;133:493-500 pubmed
    ..This study is the first report of a transcriptional activator that directly interacts with S-II and contains a transcriptional activation domain that cooperates with S-II via direct interaction. ..
  57. Shao L, Zhou H, Zhang H, Qin L, Hwa J, Yun Z, et al. SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression. Nat Commun. 2015;6:8917 pubmed publisher
    ..Mechanistic studies show that SENP1 deletion in adipocytes enhances SUMOylation of the NF-κB essential molecule, NEMO, at lysine 277/309, leading to increased NF-κB activity, cytokine production and pancreatic inflammation...
  58. Chen H, Wu Y, Zhang Y, Jin L, Luo L, Xue B, et al. Hsp70 inhibits lipopolysaccharide-induced NF-kappaB activation by interacting with TRAF6 and inhibiting its ubiquitination. FEBS Lett. 2006;580:3145-52 pubmed
  59. Viaud S, Daillère R, Boneca I, Lepage P, Langella P, Chamaillard M, et al. Gut microbiome and anticancer immune response: really hot Sh*t!. Cell Death Differ. 2015;22:199-214 pubmed publisher
    ..These findings represent a paradigm shift in our understanding of the mode of action of many compounds having an impact on the host-microbe mutualism. ..
  60. Zhou L, Yeo A, Ballarano C, Weber U, Allen K, Gilmore T, et al. Disulfide-mediated stabilization of the IκB kinase binding domain of NF-κB essential modulator (NEMO). Biochemistry. 2014;53:7929-44 pubmed publisher
    Human NEMO (NF-κB essential modulator) is a 419 residue scaffolding protein that, together with catalytic subunits IKKα and IKKβ, forms the IκB kinase (IKK) complex, a key regulator of NF-κB pathway signaling...
  61. Cui J, Zhu L, Xia X, Wang H, Legras X, Hong J, et al. NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell. 2010;141:483-96 pubmed publisher
    ..Our findings identify NLRC5 as a negative regulator that blocks two central components of the NF-kappaB and type I interferon signaling pathways and suggest an important role for NLRC5 in homeostatic control of innate immunity. ..
  62. Müller Rischart A, Pilsl A, Beaudette P, Patra M, Hadian K, Funke M, et al. The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Mol Cell. 2013;49:908-21 pubmed publisher
    ..to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-?B essential modulator (NEMO), which is essential for canonical NF-?B signaling...
  63. Qin J, Yao J, Cui G, Xiao H, Kim T, Fraczek J, et al. TLR8-mediated NF-kappaB and JNK activation are TAK1-independent and MEKK3-dependent. J Biol Chem. 2006;281:21013-21 pubmed
    ..We postulate that TLR8-mediated MEKK3-dependent IKKgamma phosphorylation might play an important role in the activation of IKK complex, leading to IkappaBalpha phosphorylation. ..
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    Nuclear factor ?B (NF-?B) essential modulator (NEMO), a regulatory component of the I?B kinase (IKK) complex, controls NF-?B activation through its interaction with ubiquitin chains...
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    ..As previously published, genetic inhibition of the NF-κB essential modulator (NEMO) in podocytes does not affect glomerular function under physiological, nonstressed conditions nor does it alter the ..
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    Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP)...
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