Defective nuclear IKKα function in patients with ectodermal dysplasia with immune deficiency

Journal of Clinical Investigation

Volumn 122, Issue 1, 2012, Pages 315-326

  Temmerman, Stephane T ^a,f   Ma, Chi A ^a   Zhao, Yongge ^a   Keenan, Jeffrey ^a   Aksentijevich, Ivona ^b   Fessler, Margaret ^a   Brown, Margaret R ^c   Knutsen, Alan ^d   Shapiro, Ralph ^e   Jain, Ashish ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

^d SAINT LOUIS UNIVERSITY   (United States)

^e Midwest Immunology Clinic   (United States)

^f UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; APC PROTEIN; CD14 ANTIGEN; CD19 ANTIGEN; CD3 ANTIGEN; CD4 ANTIGEN; CD56 ANTIGEN; CD8 ANTIGEN; CYTOKINE; HETERODIMER; HISTONE H3; I KAPPA B; I KAPPA B KINASE ALPHA; I KAPPA B KINASE GAMMA; IMMUNOGLOBULIN; IMMUNOGLOBULIN D; IMMUNOGLOBULIN M; INTERLEUKIN 12; LIPOPOLYSACCHARIDE; SULFAMETHIZOLE; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR; TRIMETHOPRIM;

ADOLESCENT; ALLOGENIC BONE MARROW TRANSPLANTATION; ARTICLE; ASTHMA; B LYMPHOCYTE; CASE REPORT; CELL ACTIVATION; CELLULITIS; CHILD; CHILD HOSPITALIZATION; CHROMOSOME ABERRATION; CONTROLLED STUDY; CYTOPLASM; ECTODERMAL DYSPLASIA; ECZEMA; ENTERIC FEEDING; EOSINOPHILIC COLITIS; GASTROINTESTINAL SYMPTOM; GENETIC CODE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNE DEFICIENCY; IMMUNOTHERAPY; INFECTION COMPLICATION; INFECTIOUS COMPLICATION; MALE; MONOCYTE; NUTRITIONAL DEFICIENCY; PNEUMOCOCCAL MENINGITIS; PNEUMOCYSTIS PNEUMONIA; PNEUMONIA; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN DEFECT; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SEPSIS; SIGNAL TRANSDUCTION; SKIN BIOPSY;

ADOLESCENT; CELL LINE; CELL NUCLEUS; CHILD, PRESCHOOL; CYTOKINES; DNA-BINDING PROTEINS; ECTODERMAL DYSPLASIA; GENE EXPRESSION; GENE KNOCKDOWN TECHNIQUES; GENE REARRANGEMENT; GENETIC DISEASES, X-LINKED; HUMANS; I-KAPPA B KINASE; IMMUNOLOGIC DEFICIENCY SYNDROMES; INTERLEUKIN-12; MALE; MAP KINASE SIGNALING SYSTEM; MONOCYTES; NF-KAPPA B; NUCLEAR PROTEINS; PROMOTER REGIONS, GENETIC; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4; TRANSCRIPTION FACTOR RELA;

EID: 84855431999     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI42534     Document Type: Article

References (34)

1. Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell. 1997;91(2):243-252. (Pubitemid 27456391)
2. Hayden MS, Ghosh S. Signaling to NF-κB. Genes Dev. 2004;18(18):2195-2224.
3. Hacker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006;2006(357):re13.
4. Birbach A, Gold P, Binder BR, Hofer E, de Martin R, Schmid JA. Signaling molecules of the NF-κB pathway shuttle constitutively between cytoplasm and nucleus. J Biol Chem. 2002;277(13):10842-10851. (Pubitemid 34952838)
5. Hu Y, et al. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKα subunit of IκB kinase. Science. 1999;284(5412):316-320.
6. Senftleben U, et al. Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway. Science. 2001;293(5534):1495-1499. (Pubitemid 32801552)
7. Bonizzi G, et al. Activation of IKKα target genes depends on recognition of specific κB binding sites by RelB:p52 dimers. EMBO J. 2004;23(21):4202-4210. (Pubitemid 39546158)
8. Dejardin E, et al. The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways. Immunity. 2002;17(4):525-535. (Pubitemid 35223540)
9. Gloire G, et al. Promoter-dependent effect of IKKα on NF-κB/p65 DNA binding. J Biol Chem. 2007;282(29):21308-21318. (Pubitemid 47099906)
10. Yamamoto Y, Verma UN, Prajapati S, Kwak YT, Gaynor RB. Histone H3 phosphorylation by IKK-αis critical for cytokine-induced gene expression. Nature. 2003;423(6940):655-659. (Pubitemid 36713227)
11. Park KJ, Krishnan V, O'Malley BW, Yamamoto Y, Gaynor RB. Formation of an IKKα-dependent transcription complex is required for estrogen receptor-mediated gene activation. Mol Cell. 2005;18(1):71-82. (Pubitemid 40444649)
12. Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS. A nucleosomal function for IkappaB kinase-alpha in NF-κB-dependent gene expression. Nature. 2003;423(6940):659-663. (Pubitemid 36713228)
13. Smahi A, et al. Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature. 2000;405(6785):466-472.
14. Doffinger R, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling. Nat Genet. 2001;27(3):277-285. (Pubitemid 32201848)
15. Jain A, Ma CA, Liu S, Brown M, Cohen J, Strober W. Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. Nat Immunol. 2001;2(3):223-228. (Pubitemid 33705998)
16. Zonana J, et al. 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). Am J Hum Genet. 2000;67(6):1555-1562.
17. Jain A, et al. Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation. J Clin Invest. 2004;114(11):1593-1602. (Pubitemid 40385550)
18. Temmerman ST, et al. Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ubiquitination. Blood. 2006;108(7):2324-2331. (Pubitemid 44497516)
19. Nishikomori R, et al. X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival. Blood. 2004;103(12):4565-4572. (Pubitemid 38745984)
20. Aradhya S, et al. Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes. Hum Mol Genet. 2001;10(22):2557-2567. (Pubitemid 33095006)
21. Ma CA, et al. Dendritic cells from humans with hypomorphic mutations in NEMO have impaired mitogen-activated protein kinase activity [published online ahead of print January 25, 2011]. Hum Mutat. doi:10.1002/humu.21439.
22. Marienfeld RB, Palkowitsch L, Ghosh S. Dimerization of the I kappa B kinase-binding domain of NEMO is required for tumor necrosis factor α-induced NF-κB activity. Mol Cell Biol. 2006;26(24):9209-9219. (Pubitemid 44904417)
23. Ea CK, Deng L, Xia ZP, Pineda G, Chen ZJ. Activation of IKK by TNF-alpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006;22(2):245-257.
24. Wu CJ, Conze DB, Li T, Srinivasula SM, Ashwell JD. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-κB activation [corrected]. Nat Cell Biol. 2006;8(4):398-406.
25. Zhou H, et al. Bcl10 activates the NF-κB pathway through ubiquitination of NEMO. Nature. 2004;427(6970):167-171. (Pubitemid 38094958)
26. Huang TT, Wuerzberger-Davis SM, Wu ZH, Miyamoto S. Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell. 2003;115(5):565-576. (Pubitemid 37506045)
27. Wu ZH, Shi Y, Tibbetts RS, Miyamoto S. Molecular linkage between the kinase ATM and NF-κB signaling in response to genotoxic stimuli. Science. 2006;311(5764):1141-1146.
28. Niu J, Shi Y, Iwai K, Wu ZH. LUBAC regulates NF-κB activation upon genotoxic stress by promoting linear ubiquitination of NEMO. EMBO J. 2011;30(18):3741-3753.
29. Johnson C, Van Antwerp D, Hope TJ. An N-terminal nuclear export signal is required for the nucleocytoplasmic shuttling of IκBα. EMBO J. 1999;18(23):6682-6693.
30. Rodriguez MS, Thompson J, Hay RT, Dargemont C. Nuclear retention of IκBα protects it from signal-induced degradation and inhibits nuclear factor κB transcriptional activation. J Biol Chem. 1999;274(13):9108-9115. (Pubitemid 29164718)
31. Tam WF, Lee LH, Davis L, Sen R. Cytoplasmic sequestration of rel proteins by IκBα requires CRM1-dependent nuclear export. Mol Cell Biol. 2000;20(6):2269-2284. (Pubitemid 30123842)
32. Verma UN, Yamamoto Y, Prajapati S, Gaynor RB. Nuclear role of I κ B Kinase-gamma/NF-κB essential modulator (IKKgamma/NEMO) in NF-κB-dependent gene expression. J Biol Chem. 2004;279(5):3509-3515. (Pubitemid 38140590)
33. Mooster JL, et al. Immune deficiency caused by impaired expression of nuclear factor-κB essential modifier (NEMO) because of a mutation in the 5′ untranslated region of the NEMO gene. J Allergy Clin Immunol. 2010;126(1):127-132.
34. Siggs OM, et al. A mutation of Ikbkg causes immune deficiency without impairing degradation of IκBα. Proc Natl Acad Sci U S A. 2010;107(7):3046-3051.