Chuk

Summary

Gene Symbol: Chuk
Description: conserved helix-loop-helix ubiquitous kinase
Alias: AI256658, Chuk1, Fbx24, Fbxo24, IKBKA, IKK alpha, IKK1, Ikka, NFKBIKA, inhibitor of nuclear factor kappa-B kinase subunit alpha, I kappa B kinase 1, I-kappa-B kinase alpha, IkappaB kinase alpha, nuclear factor NF-kappa-B inhibitor kinase alpha
Species: mouse
Products:     Chuk

Top Publications

  1. Koster M, Dai D, Marinari B, Sano Y, Costanzo A, Karin M, et al. p63 induces key target genes required for epidermal morphogenesis. Proc Natl Acad Sci U S A. 2007;104:3255-60 pubmed
    ..Our data provide insights into the role of DeltaNp63alpha in epidermal morphogenesis and homeostasis, and may contribute to our understanding of the pathogenic mechanisms underlying disorders caused by p63 mutations. ..
  2. Connelly M, Marcu K. CHUK, a new member of the helix-loop-helix and leucine zipper families of interacting proteins, contains a serine-threonine kinase catalytic domain. Cell Mol Biol Res. 1995;41:537-49 pubmed
    ..This new gene, CHUK (conserved helix-loop-helix ubiquitous kinase), may represent the founding member of a new class of interacting ..
  3. Luo J, Tan W, Ricono J, Korchynskyi O, Zhang M, Gonias S, et al. Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin. Nature. 2007;446:690-4 pubmed
    ..Yet a mechanistic link between inflammation and metastasis is missing. We identified a role for IkappaB kinase alpha (IKKalpha), activated by receptor activator of NF-kappaB (RANK/TNFRSF11A), in mammary epithelial ..
  4. Senftleben U, Cao Y, Xiao G, Greten F, Krahn G, Bonizzi G, et al. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 2001;293:1495-9 pubmed
    ..IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation. ..
  5. 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
    ..These results provide a mechanism for NEMO's critical role in IKK activation, and a key to understanding the link between cytokine-receptor proximal signalling and IKK and NF-kappaB activation. ..
  6. 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
    ..These results indicate that LUBAC is involved in the physiological regulation of the canonical NF-kappaB activation pathway through linear polyubiquitylation of NEMO. ..
  7. Matsuzawa A, Tseng P, Vallabhapurapu S, Luo J, Zhang W, Wang H, et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science. 2008;321:663-8 pubmed publisher
    ..This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling. ..
  8. Adli M, Merkhofer E, Cogswell P, Baldwin A. IKKalpha and IKKbeta each function to regulate NF-kappaB activation in the TNF-induced/canonical pathway. PLoS ONE. 2010;5:e9428 pubmed publisher
    ..These results demonstrate the importance of IKKalpha in canonical NF-kappaB activation, downstream of cytokine treatment of cells. The experiments suggest that IKKalpha will be a therapeutic target in inflammatory disorders. ..
  9. Shembade N, Pujari R, Harhaj N, Abbott D, Harhaj E. The kinase IKK? inhibits activation of the transcription factor NF-?B by phosphorylating the regulatory molecule TAX1BP1. Nat Immunol. 2011;12:834-43 pubmed publisher
    ..IKK? therefore serves a key role in the negative feedback of NF-?B canonical signaling by orchestrating assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation. ..
  10. Bakkar N, Wang J, Ladner K, Wang H, Dahlman J, Carathers M, et al. IKK/NF-kappaB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis. J Cell Biol. 2008;180:787-802 pubmed publisher
    ..Together, these data reveal a unique IKK/NF-kappaB signaling switch that functions to both inhibit differentiation and promote myotube homeostasis. ..

Detail Information

Publications63

  1. Koster M, Dai D, Marinari B, Sano Y, Costanzo A, Karin M, et al. p63 induces key target genes required for epidermal morphogenesis. Proc Natl Acad Sci U S A. 2007;104:3255-60 pubmed
    ..Our data provide insights into the role of DeltaNp63alpha in epidermal morphogenesis and homeostasis, and may contribute to our understanding of the pathogenic mechanisms underlying disorders caused by p63 mutations. ..
  2. Connelly M, Marcu K. CHUK, a new member of the helix-loop-helix and leucine zipper families of interacting proteins, contains a serine-threonine kinase catalytic domain. Cell Mol Biol Res. 1995;41:537-49 pubmed
    ..This new gene, CHUK (conserved helix-loop-helix ubiquitous kinase), may represent the founding member of a new class of interacting ..
  3. Luo J, Tan W, Ricono J, Korchynskyi O, Zhang M, Gonias S, et al. Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin. Nature. 2007;446:690-4 pubmed
    ..Yet a mechanistic link between inflammation and metastasis is missing. We identified a role for IkappaB kinase alpha (IKKalpha), activated by receptor activator of NF-kappaB (RANK/TNFRSF11A), in mammary epithelial ..
  4. Senftleben U, Cao Y, Xiao G, Greten F, Krahn G, Bonizzi G, et al. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 2001;293:1495-9 pubmed
    ..IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation. ..
  5. 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
    ..These results provide a mechanism for NEMO's critical role in IKK activation, and a key to understanding the link between cytokine-receptor proximal signalling and IKK and NF-kappaB activation. ..
  6. 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
    ..These results indicate that LUBAC is involved in the physiological regulation of the canonical NF-kappaB activation pathway through linear polyubiquitylation of NEMO. ..
  7. Matsuzawa A, Tseng P, Vallabhapurapu S, Luo J, Zhang W, Wang H, et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science. 2008;321:663-8 pubmed publisher
    ..This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling. ..
  8. Adli M, Merkhofer E, Cogswell P, Baldwin A. IKKalpha and IKKbeta each function to regulate NF-kappaB activation in the TNF-induced/canonical pathway. PLoS ONE. 2010;5:e9428 pubmed publisher
    ..These results demonstrate the importance of IKKalpha in canonical NF-kappaB activation, downstream of cytokine treatment of cells. The experiments suggest that IKKalpha will be a therapeutic target in inflammatory disorders. ..
  9. Shembade N, Pujari R, Harhaj N, Abbott D, Harhaj E. The kinase IKK? inhibits activation of the transcription factor NF-?B by phosphorylating the regulatory molecule TAX1BP1. Nat Immunol. 2011;12:834-43 pubmed publisher
    ..IKK? therefore serves a key role in the negative feedback of NF-?B canonical signaling by orchestrating assembly of the A20 ubiquitin-editing complex to limit inflammatory gene activation. ..
  10. Bakkar N, Wang J, Ladner K, Wang H, Dahlman J, Carathers M, et al. IKK/NF-kappaB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis. J Cell Biol. 2008;180:787-802 pubmed publisher
    ..Together, these data reveal a unique IKK/NF-kappaB signaling switch that functions to both inhibit differentiation and promote myotube homeostasis. ..
  11. Ingraham C, Kinoshita A, Kondo S, Yang B, Sajan S, Trout K, et al. Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet. 2006;38:1335-40 pubmed
    ..Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a new role for an IRF family member in epidermal development. ..
  12. Chung S, Sundar I, Yao H, Ho Y, Rahman I. Glutaredoxin 1 regulates cigarette smoke-mediated lung inflammation through differential modulation of I{kappa}B kinases in mice: impact on histone acetylation. Am J Physiol Lung Cell Mol Physiol. 2010;299:L192-203 pubmed publisher
  13. Liu B, Xia X, Zhu F, Park E, Carbajal S, Kiguchi K, et al. IKKalpha is required to maintain skin homeostasis and prevent skin cancer. Cancer Cell. 2008;14:212-25 pubmed publisher
    ..Thus, IKKalpha serves as an innate surveillant. ..
  14. Li Q, Lu Q, Bottero V, Estepa G, Morrison L, Mercurio F, et al. Enhanced NF-kappaB activation and cellular function in macrophages lacking IkappaB kinase 1 (IKK1). Proc Natl Acad Sci U S A. 2005;102:12425-30 pubmed
    ..Because IKK1-/- mice died at birth, we differentiated functional macrophages from embryonic day 15.5 IKK1 mutant embryonic liver...
  15. Descargues P, Sil A, Sano Y, Korchynskyi O, Han G, Owens P, et al. IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation. Proc Natl Acad Sci U S A. 2008;105:2487-92 pubmed publisher
    Cell-cycle exit and differentiation of suprabasal epidermal keratinocytes require nuclear IkappaB kinase alpha (IKKalpha), but not its protein kinase activity...
  16. Ghosh S, May M, Kopp E. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225-60 pubmed
    ..In this review, we discuss some of these recent findings and their implications for the study of NF-kappa B. ..
  17. McKenzie F, Connelly M, Balzarano D, Muller J, Geleziunas R, Marcu K. Functional isoforms of IkappaB kinase alpha (IKKalpha) lacking leucine zipper and helix-loop-helix domains reveal that IKKalpha and IKKbeta have different activation requirements. Mol Cell Biol. 2000;20:2635-49 pubmed
    ..Site-specific serine phosphorylation of IkappaBs by two IkappaB kinases (IKKalpha [also known as CHUK] and IKKbeta) targets them for proteolysis...
  18. 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
  19. Song L, Dong W, Gao M, Li J, Hu M, Guo N, et al. A novel role of IKKalpha in the mediation of UVB-induced G0/G1 cell cycle arrest response by suppressing Cyclin D1 expression. Biochim Biophys Acta. 2010;1803:323-32 pubmed publisher
    ..Notably, IKKa-dependent Cyclin D1 regulation is unrelated to IKKbeta/NF-kappaB activity...
  20. Li Q, Lu Q, Hwang J, Buscher D, Lee K, Izpisua Belmonte J, et al. IKK1-deficient mice exhibit abnormal development of skin and skeleton. Genes Dev. 1999;13:1322-8 pubmed
    IkappaB kinases (IKKs) IKK1 and IKK2 are two putative IkappaBalpha kinases involved in NF-kappaB activation. To examine the in vivo functions of IKK1, we generated IKK1-deficient mice...
  21. Delhase M, Hayakawa M, Chen Y, Karin M. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science. 1999;284:309-13 pubmed
    ..Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response. ..
  22. 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
  23. Gareus R, Huth M, Breiden B, Nenci A, Rösch N, Haase I, et al. Normal epidermal differentiation but impaired skin-barrier formation upon keratinocyte-restricted IKK1 ablation. Nat Cell Biol. 2007;9:461-9 pubmed
    The kinase IKK1 (also known as IKKalpha) was previously reported to regulate epidermal development and skeletal morphogenesis by acting in keratinocytes to induce their differentiation in an NF-kappaB independent manner...
  24. Moreno Maldonado R, Ramirez A, Navarro M, Fernández Aceñero M, Villanueva C, Page A, et al. IKKalpha enhances human keratinocyte differentiation and determines the histological variant of epidermal squamous cell carcinomas. Cell Cycle. 2008;7:2021-9 pubmed
    ..The tight correlation between the properties of both murine and human ASCC variants strongly suggests that IKKalpha is responsible for the development of this human SCC variant. ..
  25. Song L, Li J, Hu M, Huang C. Both IKKalpha and IKKbeta are implicated in the arsenite-induced AP-1 transactivation correlating with cell apoptosis through NF-kappaB activity-independent manner. Exp Cell Res. 2008;314:2187-98 pubmed publisher
    ..Therefore, we concluded that both IKKalpha and IKKbeta can mediate arsenite-induced AP-1 transactivation through NF-kappaB activity-independent manner. ..
  26. Balkhi M, Willette Brown J, Zhu F, Chen Z, Liu S, Guttridge D, et al. IKK?-mediated signaling circuitry regulates early B lymphopoiesis during hematopoiesis. Blood. 2012;119:5467-77 pubmed publisher
    ..The results of the present study demonstrate that IKK? regulates B-lineage commitment via combined canonical and noncanonical NF-?B transcriptional activities to target Pax5 expression during hematopoiesis. ..
  27. Li N, Wu X, Holzer R, Lee J, Todoric J, Park E, et al. Loss of acinar cell IKK? triggers spontaneous pancreatitis in mice. J Clin Invest. 2013;123:2231-43 pubmed publisher
  28. Lawrence T, Bebien M, Liu G, Nizet V, Karin M. IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation. Nature. 2005;434:1138-43 pubmed
    ..Inactivation of IKKalpha in mice enhances inflammation and bacterial clearance. Hence, the two IKK catalytic subunits have evolved opposing but complimentary roles needed for the intricate control of inflammation and innate immunity. ..
  29. 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
    ..Here, we show that the two IkappaB kinases, IKK1/IKKalpha and IKK2/IKKbeta, display distinct collaborative and specific functions that are essential to protect the ..
  30. Yang S, Yao H, Rajendrasozhan S, Chung S, Edirisinghe I, Valvo S, et al. RelB is differentially regulated by IkappaB Kinase-alpha in B cells and mouse lung by cigarette smoke. Am J Respir Cell Mol Biol. 2009;40:147-58 pubmed publisher
    ..Rapid degradation of RelB signals for RelA/p65 activation and loss of its protective ability to suppress the proinflammatory cytokine release in lymphoid B cells. ..
  31. Mancino A, Habbeddine M, Johnson E, Luron L, Bebien M, Memet S, et al. I kappa B kinase alpha (IKK?) activity is required for functional maturation of dendritic cells and acquired immunity to infection. EMBO J. 2013;32:816-28 pubmed publisher
    ..The serine/threonine kinase IKK? (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity...
  32. Zhu F, Xia X, Liu B, Shen J, Hu Y, Person M, et al. IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Mol Cell. 2007;27:214-27 pubmed
    ..Thus, IKKalpha protects the 14-3-3sigma locus from hypermethylation, which serves as a mechanism of maintaining genomic stability in keratinocytes. ..
  33. Liu B, Yang Y, Chernishof V, Loo R, Jang H, Tahk S, et al. Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to restrict inflammation and immunity. Cell. 2007;129:903-14 pubmed
    ..Our results identify a signaling pathway in which proinflammatory stimuli activate the IKKalpha-mediated sumoylation-dependent phosphorylation of PIAS1 for the immediate repression of inflammatory gene activation. ..
  34. Nakano H, Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H, et al. Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc Natl Acad Sci U S A. 1998;95:3537-42 pubmed
  35. Li Q, Estepa G, Memet S, Israel A, Verma I. Complete lack of NF-kappaB activity in IKK1 and IKK2 double-deficient mice: additional defect in neurulation. Genes Dev. 2000;14:1729-33 pubmed
    NF-kappaB activity is induced by cytokines, stress, and pathogens. IKK1 and IKK2 are critical IkappaB kinases in NF-kappaB activation. In this study mice lacking IKK1 and IKK2 died at E12...
  36. Richardson R, Dixon J, Malhotra S, Hardman M, Knowles L, Boot Handford R, et al. Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat Genet. 2006;38:1329-34 pubmed
    ..Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process. ..
  37. Takeda K, Takeuchi O, Tsujimura T, Itami S, Adachi O, Kawai T, et al. Limb and skin abnormalities in mice lacking IKKalpha. Science. 1999;284:313-6 pubmed
    The gene encoding inhibitor of kappa B (IkappaB) kinase alpha (IKKalpha; also called IKK1) was disrupted by gene targeting. IKKalpha-deficient mice died perinatally...
  38. Matsushima A, Kaisho T, Rennert P, Nakano H, Kurosawa K, Uchida D, et al. Essential role of nuclear factor (NF)-kappaB-inducing kinase and inhibitor of kappaB (IkappaB) kinase alpha in NF-kappaB activation through lymphotoxin beta receptor, but not through tumor necrosis factor receptor I. J Exp Med. 2001;193:631-6 pubmed
    ..These results demonstrate that both NIK and IKKalpha are essential for the induction of NF-kappaB through LTbetaR, whereas the NIK-IKKalpha pathway is dispensable in TNFR-I signaling. ..
  39. Hacker H, Chi L, Rehg J, Redecke V. NIK prevents the development of hypereosinophilic syndrome-like disease in mice independent of IKK? activation. J Immunol. 2012;188:4602-10 pubmed publisher
    ..Our data show that NIK activity in nonhematopoietic cells controls Th2 cell development and prevents eosinophil-driven inflammatory disease, most likely using a signaling pathway that operates independent of the known NIK substrate IKK?...
  40. Park E, Zhu F, Liu B, Xia X, Shen J, Bustos T, et al. Reduction in IkappaB kinase alpha expression promotes the development of skin papillomas and carcinomas. Cancer Res. 2007;67:9158-68 pubmed
    We reported recently a marked reduction in IkappaB kinase alpha (IKKalpha) expression in a large proportion of human poorly differentiated squamous cell carcinomas (SCC) and the occurrence of Ikkalpha mutations in human SCCs...
  41. Hu Y, Baud V, Delhase M, Zhang P, Deerinck T, Ellisman M, et al. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase. Science. 1999;284:316-20 pubmed
    ..Instead, loss of IKKalpha interfered with multiple morphogenetic events, including limb and skeletal patterning and proliferation and differentiation of epidermal keratinocytes. ..
  42. Yoshida K, Hu Y, Karin M. IkappaB kinase alpha is essential for development of the mammalian cornea and conjunctiva. Invest Ophthalmol Vis Sci. 2000;41:3665-9 pubmed
    To determine the requirement of IkappaB kinase alpha (Ikkalpha) for differentiation of the mammalian cornea and conjunctiva...
  43. Hoshino K, Sugiyama T, Matsumoto M, Tanaka T, Saito M, Hemmi H, et al. IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9. Nature. 2006;440:949-53 pubmed
    ..Furthermore, IKK-alpha associated with and phosphorylated IRF-7. Our results identify a role for IKK-alpha in TLR7/9 signalling, and highlight IKK-alpha as a potential target for manipulating TLR-induced IFN-alpha production. ..
  44. Song Y, Kim M, Kim H, Jung B, Yang J, Narasimhan P, et al. Oxidative stress increases phosphorylation of IkappaB kinase-alpha by enhancing NF-kappaB-inducing kinase after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2010;30:1265-74 pubmed publisher
    ..These results suggest that augmentation of NIK, IKKalpha, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke). ..
  45. Gloire G, Horion J, El Mjiyad N, Bex F, Chariot A, Dejardin E, et al. Promoter-dependent effect of IKKalpha on NF-kappaB/p65 DNA binding. J Biol Chem. 2007;282:21308-18 pubmed
    ..We conclude that nuclear IKKalpha is required for p65 DNA binding in a gene-specific manner. ..
  46. Yamamoto Y, Verma U, Prajapati S, Kwak Y, Gaynor R. Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression. Nature. 2003;423:655-9 pubmed
    ..These results define a new nuclear role of IKK-alpha in modifying histone function that is critical for the activation of NF-kappaB-directed gene expression. ..
  47. Bonizzi G, Bebien M, Otero D, Johnson Vroom K, Cao Y, Vu D, et al. Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. EMBO J. 2004;23:4202-10 pubmed
    ..This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway. ..
  48. Maeda S, Kamata H, Luo J, Leffert H, Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell. 2005;121:977-90 pubmed
    ..IKKbeta, therefore, orchestrates inflammatory crosstalk between hepatocytes and hematopoietic-derived cells that promotes chemical hepatocarcinogenesis. ..
  49. Enzler T, Bonizzi G, Silverman G, Otero D, Widhopf G, Anzelon Mills A, et al. Alternative and classical NF-kappa B signaling retain autoreactive B cells in the splenic marginal zone and result in lupus-like disease. Immunity. 2006;25:403-15 pubmed
    ..Thus, both classical and alternative NF-kappaB signaling are important for development of lupus-like disease associated with BAFF overproduction. The same mechanisms may be involved in the pathogenesis of human SLE. ..
  50. Descargues P, Sil A, Karin M. IKKalpha, a critical regulator of epidermal differentiation and a suppressor of skin cancer. EMBO J. 2008;27:2639-47 pubmed publisher
    b>IkappaB kinase alpha (IKKalpha), one of the two catalytic subunits of the IKK complex involved in nuclear factor kappaB (NF-kappaB) activation, also functions as a molecular switch that controls epidermal differentiation...
  51. Yang S, Valvo S, Yao H, Kode A, Rajendrasozhan S, Edirisinghe I, et al. IKK alpha causes chromatin modification on pro-inflammatory genes by cigarette smoke in mouse lung. Am J Respir Cell Mol Biol. 2008;38:689-98 pubmed publisher
    ..active NF-kappaB (RelA/p65-p50) in the nucleus and transcription of pro-inflammatory genes, whereas the role of IKK alpha in perpetuation of sustained inflammatory response is not known...
  52. Anest V, Hanson J, Cogswell P, Steinbrecher K, Strahl B, Baldwin A. A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene expression. Nature. 2003;423:659-63 pubmed
    ..These findings provide additional insight into the role of the IKK complex in NF-kappaB-regulated gene expression. ..
  53. Xiao Z, Jiang Q, Willette Brown J, Xi S, Zhu F, Burkett S, et al. The pivotal role of IKKα in the development of spontaneous lung squamous cell carcinomas. Cancer Cell. 2013;23:527-40 pubmed publisher
    ..This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs. ..
  54. Massa P, Li X, Hanidu A, Siamas J, Pariali M, Pareja J, et al. Gene expression profiling in conjunction with physiological rescues of IKKalpha-null cells with wild type or mutant IKKalpha reveals distinct classes of IKKalpha/NF-kappaB-dependent genes. J Biol Chem. 2005;280:14057-69 pubmed
  55. Kaisho T, Takeda K, Tsujimura T, Kawai T, Nomura F, Terada N, et al. IkappaB kinase alpha is essential for mature B cell development and function. J Exp Med. 2001;193:417-26 pubmed
    ..Taken together, these results demonstrate that IKKalpha is critically involved in the prevention of cell death and functional development of mature B cells. ..
  56. Penzo M, Molteni R, Suda T, Samaniego S, Raucci A, Habiel D, et al. Inhibitor of NF-kappa B kinases alpha and beta are both essential for high mobility group box 1-mediated chemotaxis [corrected]. J Immunol. 2010;184:4497-509 pubmed publisher
    ..Thus, proinflammatory HMGB1 chemotactic responses mechanistically require the differential collaboration of both IKK-dependent NF-kappaB signaling pathways. ..
  57. Chaisson M, Branstetter D, Derry J, Armstrong A, Tometsko M, Takeda K, et al. Osteoclast differentiation is impaired in the absence of inhibitor of kappa B kinase alpha. J Biol Chem. 2004;279:54841-8 pubmed
    ..Mice expressing a kinase-inactive form of the inhibitor of kappa B kinase alpha (IKK alpha) have mammary gland defects similar to those of RANK-null mice yet have apparently normal osteoclast function...
  58. Cao Y, Bonizzi G, Seagroves T, Greten F, Johnson R, Schmidt E, et al. IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell. 2001;107:763-75 pubmed
    ..Thus, IKKalpha is a critical intermediate in a pathway that controls mammary epithelial proliferation in response to RANK signaling via cyclin D1. ..
  59. Ghosh A, Roy A, Liu X, Kordower J, Mufson E, Hartley D, et al. Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A. 2007;104:18754-9 pubmed
    ..evaluates the ability of peptide corresponding to the NF-kappaB essential modifier-binding domain (NBD) of IkappaB kinase alpha (IKKalpha) or IKKbeta to prevent nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-..
  60. Liu B, Park E, Zhu F, Bustos T, Liu J, Shen J, et al. A critical role for I kappaB kinase alpha in the development of human and mouse squamous cell carcinomas. Proc Natl Acad Sci U S A. 2006;103:17202-7 pubmed
    ..Thus, overexpression of IKKalpha in the epidermis antagonized chemical carcinogen-induced mitogenic and angiogenic activities, repressing tumor progression and metastases. ..
  61. Ruocco M, Maeda S, Park J, Lawrence T, Hsu L, Cao Y, et al. I{kappa}B kinase (IKK){beta}, but not IKK{alpha}, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. J Exp Med. 2005;201:1677-87 pubmed
    ..IKKbeta also protects osteoclasts and their progenitors from tumor necrosis factor alpha-induced apoptosis, and its loss in hematopoietic cells prevents inflammation-induced bone loss. ..
  62. Li X, Massa P, Hanidu A, Peet G, Aro P, Savitt A, et al. IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program. J Biol Chem. 2002;277:45129-40 pubmed
    ..SOCS-3, a negative effector of STAT3 signaling, was found to be an NF-kappaB/IKK-induced gene, suggesting that IKK-mediated NF-kappaB activation can coordinately illicit negative effects on STAT signaling. ..
  63. Hoshino K, Sasaki I, Sugiyama T, Yano T, Yamazaki C, Yasui T, et al. Critical role of IkappaB Kinase alpha in TLR7/9-induced type I IFN production by conventional dendritic cells. J Immunol. 2010;184:3341-5 pubmed publisher
    ..b>IkappaB kinase alpha (IKKalpha) is critically involved in this type I IFN production through its interaction with IFN regulatory ..