DOCSLIB.ORG

Association of SUMO4 M55V and -94Ins/Del Gene Variants with Type-2 Diabetes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Association of SUMO4 M55V and -94Ins/Del Gene Variants with Type-2 Diabetes in vivo 28: 919-924 (2014) Association of SUMO4 M55V and -94Ins/Del Gene Variants with Type-2 Diabetes SEYMA SOZEN1, CEM HOROZOGLU1, ELIF SINEM BIRELLER1, ZEYNEP KARAALI2 and BEDIA CAKMAKOGLU1 1Department of Molecular Medicine, Institute for Experimental Medicine Research, Istanbul University, Istanbul, Turkey; 2Department of Internal Medicine, Haseki Training and Research Hospital, Istanbul, Turkey Abstract. Aim: There are two different types of diabetes suggested a common underlying genetic basis (2, 3). To date, mellitus, type 1 and type 2, with still unclear molecular only some shared susceptibility genes have been reported. mechanisms. In the present study, we aimed to investigate the Ikegami and Ogihara have indicated that type-1 diabetes is role of small ubiquitin-like modifier 4 (SUMO4) M55V and the result of an absolute loss of endogenous insulin due to nuclear factor kappa B1 (NFKB1)-94del/ins in type-2 its autoimmune destruction of insulin-producing cells of the diabetes mellitus. Materials and Methods: We analyzed pancreas, whereas type-2 diabetes occurs due to de-regulated SUMO4 M55V and NFKB1-94del/ins variants in 104 insulin secretion and/or insulin sensitivity and shows patients with type-2 diabetes and 124 healthy controls using variability within each individual (1). The human leukocyte the polymerase chain reaction (PCR) and restriction antigen (HLA) region for insulin-dependent diabetes mellitus fragment length polymorphism (RFLP) techniques. Results: 1 (IDDM1), which is a major susceptibility locus for type-1 The number of SUMO4 M55V MM genotype and M allele diabetes, has also been associated with type-2 diabetes (4, carriers was significantly higher in patients compared to the 5). The IDDM5 locus has been mapped to an approximately control group; however, no efficiency results were found 200-kb interval on chromosome 6q25 (6, 7). This new locus related to NFΚB1-94del/ins polymorphism. Conclusion: It contains two genes, small ubiquitin-like modifier 4 (SUMO4) was found that SUMO4 M55V polymorphism and type-2 and MAPK kinase 7 interacting protein 2 (MAP3K7IP2). diabetes were significantly associated with a possible These may be involved in autoimmunity and inflammation SUMO4 region to type-2 diabetes susceptibility. This through regulation of nuclear factor kappa beta (NF-κB) and preliminary study showed that the distribution of SUMO4 heat shock transcription factor activator 6q25 (6-8). NF-κB is M55V and type-2 diabetes mellitus in Turkish patients may a transcription factor, which plays important roles in form the basis of future research. inflammation, cell survival, angiogenesis and apoptosis. It is located at the signaling pathway terminal of the activated T Diabetes mellitus, a disease described as hyperglycemia cells (9). depending on relative or absolute deficiency of circulating The SUMO4 gene is primarily expressed in the kidney and insulin, comprises of two major forms with distinct immune system (6). Because SUMO4 is located at the sixth pathogeneses, type 1 and type 2. Genetic factors including intron of the mitogen-activated protein (MAP), this location several predisposing genes and environmental effects are indirectly regulates the activation of NFκB in response to involved in both types (1). Although there are distinctive interlukin-10 (IL-10) (10, 11). SUMO4 may regulate the differences in disease pathogenesis, epidemiological data immune response through the substrate inhibitor (IkBα), a show that familial clustering of type 1 and type 2 has suppressor of NFκB, followed by activation of NFκB (7). SUMO4 is an opposite regulator of NFκB. Upstream of NFκB in the signaling pathway, ubiquitination of IkB is the premise of proteasome-mediated degradation of IkBα that Correspondence to: Bedia Cakmakoglu, Department of Molecular frees NFκB to translocate to the nucleus (12). Human SUMO Medicine, Institute for Experimental Medicine Research, Istanbul protein has similar structures to ubiquitine that could University, Vakif Gureba Cad. Capa 34390, Istanbul, Turkey. Tel: conjugate at the same site on IkBα (13). +092 124142000-33305, Fax: +902 125324171, e-mail: [email protected] It has been reported that single nucleotide polymorphisms (SNPs) are related with type-1 diabetes including SUMO4 Key Words: NFKB1, polymorphism, SUMO4, type 2 diabetes. M55V located at the SUMO4/MAP3K7IP2 region in diverse 0258-851X/2014 $2.00+.40 919 in vivo 28: 919-924 (2014) ethnic groups (6, 7). Although there have been reproducible Results association data from Eastern Asian populations (14, 15), results from Caucasian populations showed disparity (6, 7). Demographic data for the study groups are given in Table I. SUMO4 M55V was considered as a causative variant of A statistically significant difference was observed in the IDDM, but with alleles carrying contrary risk (15, 16). A distribution of genotype and allele frequencies in the patient study of 404 patients with type-2 diabetes and 500 controls and control groups for SUMO4 gene polymorphism (p=0,000 in Beijing, China, revealed that carriers of the G allele of χ2=17,56 and p=0,005, χ2=7,84 respectively, Table II). SUMO4 M55V displayed greater risk for type-2 diabetes SUMO4 MV genotype in the control group was statistically (16). Moreover, G allele frequency was markedly increased higher than the patient group and this genotype was four in 403 patients with type-2 diabetes and diabetic nephropathy times more likely to protect against type 2 diabetes (p=0,000, in a study from Taiwan (17). Noso et al. obtained significant χ2=24,47, Odds Ratio (OR)=0,23, %95 Confidence Interval results from 355 Japanese patients on the relationship (CI)=0,12-0,42). SUMO4 MM genotype in the patient group between type-2 diabetes with SUMO4 (18). was also statistically higher than in the control group and this A gene expression study through microarray showed that genotype had 4.23 times higher risk for developing type 2 SUMO4 was involved in the pathogenesis of type-2 diabetes diabetes (p=0,000, χ2=21,08, OR=4,23 95% CI=2,37-8,04). and the authors nominated SUMO4 as a new therapeutic Carriers of SUMO4 V+ (VV + MV) genotype in the control target (19). Nevertheless, in Western populations no group (84,6%) was higher than in the patient group (56,5%) association has been found between this variant and type-2 and was three times more likely to protect against type-2 diabetes (13, 20, 14). diabetes (p=0,000, χ2=21,08, OR=0,23; 95% CI=0,12-0,44; Taking into consideration the functional and genetic Data not shown in table). No statistical difference was evidence, we aimed to screen for the SUMO4 M55V and observed in the distribution of genotype and allele NFKB1-94del/ins gene variants in Turkish patients with type frequencies in the patient and control groups for NFΚB1 2 diabetes mellitus. gene polymorphism (p>0.05) (Table III). Materials and Methods Discussion Subjects. In total, 228 Turkish subjects, 104 patients with type 2 In the present study we screened 104 patients with type-2 diabetes (68 women and 36 men) and 124 healthy control subjects diabetes and 124 healthy controls for SUMO4 M55V and (76 women and 48 men), were enrolled to our study. The median age of patients with type 2 diabetes and control subjects with no NFΚB1-94ins/del variants to investigate the role of genetic clinical diabetes and no family history of diabetes was 51.5±13.3 variations on the risk of type-2 diabetes. Our results showed and 48.4±10.8 years, respectively. a statistically significant difference in the distribution of genotype and allele frequencies for SUMO4 between patients DNA isolation. After obtaining written informed consent from the and controls. SUMO4 MM genotype was higher in the participants and approval from the Istanbul University’s Ethics patient group than in the controls and had 3.48-times higher Committee, blood specimens were collected in tubes containing risk for developing type-2 diabetes. On the other hand ethylenediaminetetraacetic acid (EDTA). DNA was ex¬tracted from peripheral blood lymphocytes using the salting-out procedure (21). persons who carriers of SUMO4 V allele (VV and MV) had three times protection against to type-2 diabetes. Genotyping. Polymorphisms were genotyped using polymerase chain Genome-wide studies have shown the linkage of type-2 reaction (PCR)/restriction fragment length polymorphism (RFLP) diabetes at chromosome 6q where a susceptibility gene for methods. PCR was used to amplify the region of SUMO4 M55V type 1 diabetes (1DDM5) was mapped, in African–American polymorphism and the NFKB1 94ins/del polymorphism (22, 23). (24), Chinese (25) and Finnish populations (26). Genes on PCR-RFLP with Tru1I restriction enzyme (MBI Fermentas, 6q22–26 that influence fasting serum insulin levels have also Lithuania) at 65˚C overnight and Van91I restriction enzyme (MBI been reported (27). In this respect, chromosome 6q may Fermentas, Lithuania) at 65˚C for 2 hours for SUMO4 and NFKB1, respectively, and all the final samples were evaluated using agarose harbor susceptibility genes for type 1 and type 2 diabetes. gel electrophoresis (2%). The obtained bands of 182 bp, 161 and 21 Controversial results were obtained from genotyping studies bp were evaluated as the MM, VV and MV, respectively for of distinct ethnic groups including Asians and Europeans. SUMO4. Accordingly, the bands of 254 bp, 206 and 48 bp were Noso et al. revealed the association between SUMO4 M55V evaluated as WW, DD and WD, respectively for NFKB1. variant and type-1 and type-2 diabetes (19). Studies from Japan have implied a relationship between SUMO4 variant Statistical analysis. The SPSS 11.0 software was used for statistical and type-1 diabetes in the Asian population. Moreover, other analysis (SPPS Inc., Chicago, IL, USA). Chi square test and Fisher test were used to assess the differences of genotype and allele studies have suggested the possibility of a contribution of the frequency between the two groups.
Load more

Recommended publications
  • Tak1 Polyclonal Antibody Catalog # AP72719
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Tak1 Polyclonal Antibody Catalog # AP72719 Specification Tak1 Polyclonal Antibody - Product Information Application IF Primary Accession O43318 Reactivity Human, Mouse, Rat Host Rabbit Clonality Polyclonal Tak1 Polyclonal Antibody - Additional Information Gene ID 6885 Other Names MAP3K7; TAK1; Mitogen-activated protein kinase kinase kinase 7; Transforming growth factor-beta-activated kinase 1; TGF-beta-activated kinase 1 Dilution IF~~IF: 1:50-200 Western Blot: 1/500 - 1/2000. Immunohistochemistry: 1/100 - 1/300. ELISA: 1/40000. Not yet tested in other applications. Format Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide. Storage Conditions -20℃ Tak1 Polyclonal Antibody - Protein Information Name MAP3K7 {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:6859} Function Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including Page 1/3 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7.
    [Show full text]
  • Wo 2010/075007 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 1 July 2010 (01.07.2010) WO 2010/075007 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12Q 1/68 (2006.01) G06F 19/00 (2006.01) kind of national protection available): AE, AG, AL, AM, C12N 15/12 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2009/067757 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 11 December 2009 ( 11.12.2009) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (26) Publication Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 12/3 16,877 16 December 2008 (16.12.2008) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): DODDS, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, W., Jean [US/US]; 938 Stanford Street, Santa Monica, TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, CA 90403 (US).
    [Show full text]
  • Genome-Wide Analysis of Host-Chromosome Binding Sites For
    Lu et al. Virology Journal 2010, 7:262 http://www.virologyj.com/content/7/1/262 RESEARCH Open Access Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) Fang Lu1, Priyankara Wikramasinghe1, Julie Norseen1,2, Kevin Tsai1, Pu Wang1, Louise Showe1, Ramana V Davuluri1, Paul M Lieberman1* Abstract The Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1) protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication (OriP), regulates transcription of viral and cellular genes, and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes, potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1, we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation (ChIP) combined with massively parallel deep-sequencing (ChIP-Seq) was used to identify cellular sites bound by EBNA1. Sites identified by ChIP- Seq were validated by conventional real-time PCR, and ChIP-Seq provided quantitative, high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11, between the divergent FAM55 D and FAM55B genes. A con- sensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites, sug- gesting that some of these sites are indirectly bound by EBNA1.
    [Show full text]
  • Protein Phosphorylation Sites Notes References Transcription Factors
    Protein Phosphorylation Notes References sites Transcription AML1 Ser249, Ser266 Phosphorylation of the acute myelogenous leukemia 1 (AML1) potentially regulates its (Tanaka et al., 1996) Factors (RUNX1) transactivation potential and thereby modifies myeloid hematopoietic differentiation. Androgen Ser514 Phosphorylation of androgen receptor by ERKs is controversial. May play a role in survival (Yeh et al., 1999) receptor and proliferation of prostate cells. Arix/Phox2a Ser36, Ser71 Phosphorylation of Arix by ERK1/2 inhibits its ability to interact with target genes. (Hsieh et al., 2005) ATF2 Thr71 This phosphorylation together with the phosphorylation of Thr69 by p38MAPK induces (Ouwens et al., 2002) activation of ATF2. Beta2 (Neuro Ser274 Phosphorylation of this HLH transcription factor induces its glucose-sensitive transactivation (Khoo et al. 2003) D1) and enhances its capability to heterodimerize with E47/12 and bind to DNA. BCL-6 Ser333, Ser343 Phosphorylation of BCL-6 induces its degradation that is important for B-cell differentiation (Niu et al., 1998) and antibody response. BMAL1 Ser527, Thr534, Phosphorylation of this helix-loop-helix-PAS transcription factor inhibits its activity as a clock (Sanada et al., 2002) Ser599 (chicken) oscillator. CBP Thr188 Phosphorylation of the C-terminal region of the CREB binding protein (CBP, and also its (Janknecht and homolog p300) enhances its transactivation potential. Nordheim, 1996) C/EBPb Thr188 (rat) Phosphorylation of the CCAAT/enhancer-binding protein-b (C/EBPb) by ERK2 (not ERK1) (Hanlon et al., 2001) enhances its interaction with SRF and its transactivation activity. CRY1/2 Ser265, Ser557 Phosphorylation of the Cryptochromes proteins CRY1 and 2 results in attenuation of their (Sanada et al., 2004) (CRY1, mouse) ability to inhibit BMAL1:CLOCK-mediated transcription.
    [Show full text]
  • 2219.Full.Pdf
    The JNK Are Important for Development and Survival of Macrophages S. Roy Himes, David P. Sester, Timothy Ravasi, Stephen L. Cronau, Tedjo Sasmono and David A. Hume This information is current as of September 28, 2021. J Immunol 2006; 176:2219-2228; ; doi: 10.4049/jimmunol.176.4.2219 http://www.jimmunol.org/content/176/4/2219 Downloaded from References This article cites 64 articles, 40 of which you can access for free at: http://www.jimmunol.org/content/176/4/2219.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 28, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology The JNK Are Important for Development and Survival of Macrophages S. Roy Himes, David P. Sester, Timothy Ravasi, Stephen L. Cronau, Tedjo Sasmono, and David A. Hume1 We report in this study that activation of the JNK by the growth factor, CSF-1 is critical for macrophage development, prolif- eration, and survival.
    [Show full text]
  • Table S1| Differential Expression Analysis of the Atopy Transcriptome
    Table S1| Differential expression analysis of the atopy transcriptome in CD4+ T-cell responses to allergens in atopic and nonatopic subjects Probe ID S.test Gene Symbol Gene Description Chromosome Statistic Location 7994280 10.32 IL4R Interleukin 4 receptor 16p11.2-12.1 8143383 8.95 --- --- --- 7974689 8.50 DACT1 Dapper, antagonist of beta-catenin, homolog 1 14q23.1 8102415 7.59 CAMK2D Calcium/calmodulin-dependent protein kinase II delta 4q26 7950743 7.58 RAB30 RAB30, member RAS oncogene family 11q12-q14 8136580 7.54 RAB19B GTP-binding protein RAB19B 7q34 8043504 7.45 MAL Mal, T-cell differentiation protein 2cen-q13 8087739 7.27 CISH Cytokine inducible SH2-containing protein 3p21.3 8000413 7.17 NSMCE1 Non-SMC element 1 homolog (S. cerevisiae) 16p12.1 8021301 7.15 RAB27B RAB27B, member RAS oncogene family 18q21.2 8143367 6.83 SLC37A3 Solute carrier family 37 member 3 7q34 8152976 6.65 TMEM71 Transmembrane protein 71 8q24.22 7931914 6.56 IL2R Interleukin 2 receptor, alpha 10p15-p14 8014768 6.43 PLXDC1 Plexin domain containing 1 17q21.1 8056222 6.43 DPP4 Dipeptidyl-peptidase 4 (CD26) 2q24.3 7917697 6.40 GFI1 Growth factor independent 1 1p22 7903507 6.39 FAM102B Family with sequence similarity 102, member B 1p13.3 7968236 5.96 RASL11A RAS-like, family 11, member A --- 7912537 5.95 DHRS3 Dehydrogenase/reductase (SDR family) member 3 1p36.1 7963491 5.83 KRT1 Keratin 1 (epidermolytic hyperkeratosis) 12q12-q13 7903786 5.72 CSF1 Colony stimulating factor 1 (macrophage) 1p21-p13 8019061 5.67 SGSH N-sulfoglucosamine sulfohydrolase (sulfamidase) 17q25.3
    [Show full text]
  • MAP3K7 (Phospho-Thr187) Antibody Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP52512
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 MAP3K7 (Phospho-Thr187) Antibody Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP52512 Specification MAP3K7 (Phospho-Thr187) Antibody - Product Information Application WB Primary Accession O43318 Reactivity Human, Mouse, Rat Host Rabbit Clonality Polyclonal Calculated MW 67196 MAP3K7 (Phospho-Thr187) Antibody - Additional Information Gene ID 6885 Other Names Mitogen-activated protein kinase kinase Western blot analysis of extracts from 3T3 kinase 7, Transforming growth factor-beta-activated kinase 1, cells, treated with heat shock, using MAP3K7 TGF-beta-activated kinase 1, MAP3K7, TAK1 (Phospho-Thr187) antibody. Dilution WB~~1:1000 Format Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.09% (W/V) sodium azide and 50% glycerol. Storage Conditions -20℃ MAP3K7 (Phospho-Thr187) Antibody - Protein Information Western blot analysis of extracts from 3T3 cells (Lane 2), A549 cells (Lane 3) and Hela cells (Lane 4), using MAP3K7 Name MAP3K7 (Phospho-Thr187) Antibody. The lane on the {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:6859} left is treated with synthesized peptide. Function Serine/threonine kinase which acts as an MAP3K7 (Phospho-Thr187) Antibody - essential component of the MAP kinase Background signal transduction pathway. Plays an important role in the cascades of cellular Serine/threonine kinase which acts as an Page 1/3 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 responses evoked by changes in the essential component of the MAP kinase signal environment. Mediates signal transduction transduction pathway.
    [Show full text]
  • Supplementary Material DNA Methylation in Inflammatory Pathways Modifies the Association Between BMI and Adult-Onset Non- Atopic
    Supplementary Material DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non- Atopic Asthma Ayoung Jeong 1,2, Medea Imboden 1,2, Akram Ghantous 3, Alexei Novoloaca 3, Anne-Elie Carsin 4,5,6, Manolis Kogevinas 4,5,6, Christian Schindler 1,2, Gianfranco Lovison 7, Zdenko Herceg 3, Cyrille Cuenin 3, Roel Vermeulen 8, Deborah Jarvis 9, André F. S. Amaral 9, Florian Kronenberg 10, Paolo Vineis 11,12 and Nicole Probst-Hensch 1,2,* 1 Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; [email protected] (A.J.); [email protected] (M.I.); [email protected] (C.S.) 2 Department of Public Health, University of Basel, 4001 Basel, Switzerland 3 International Agency for Research on Cancer, 69372 Lyon, France; [email protected] (A.G.); [email protected] (A.N.); [email protected] (Z.H.); [email protected] (C.C.) 4 ISGlobal, Barcelona Institute for Global Health, 08003 Barcelona, Spain; [email protected] (A.-E.C.); [email protected] (M.K.) 5 Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain 6 CIBER Epidemiología y Salud Pública (CIBERESP), 08005 Barcelona, Spain 7 Department of Economics, Business and Statistics, University of Palermo, 90128 Palermo, Italy; [email protected] 8 Environmental Epidemiology Division, Utrecht University, Institute for Risk Assessment Sciences, 3584CM Utrecht, Netherlands; [email protected] 9 Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College, SW3 6LR London, UK; [email protected] (D.J.); [email protected] (A.F.S.A.) 10 Division of Genetic Epidemiology, Medical University of Innsbruck, 6020 Innsbruck, Austria; [email protected] 11 MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, W2 1PG London, UK; [email protected] 12 Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy * Correspondence: [email protected]; Tel.: +41-61-284-8378 Int.
    [Show full text]
  • TAB2 Antibody Catalog # ASC10267
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 TAB2 Antibody Catalog # ASC10267 Specification TAB2 Antibody - Product Information Application IHC Primary Accession Q9NYJ8 Other Accession NP_055908, 14149669 Reactivity Human Host Rabbit Clonality Polyclonal Isotype IgG Application Notes TAB2 antibody can be used for detection of TAB2 by immunohistoc Immunohistochemistry of TAB2 in human hemistry at 5 brain tissue with TAB2 antibody at 5 µg/mL. µg/mL. TAB2 Antibody - Background TAB2 Antibody - Additional Information TAB2 Antibody: TAB2 is an activator of Gene ID 23118 MAP3K7/TAK1, which is required for for the IL-1 Other Names induced activation NF-kappaB and MAPK8/JNK. TAB2 Antibody: CHTD2, MAP3K7IP2, This protein forms a kinase complex with KIAA0733, TGF-beta-activated kinase 1 and TRAF6, MAP3K7 and TAB1, thus serves as an MAP3K7-binding protein 2, adaptor linking MAP3K7 and TRAF6. This Mitogen-activated protein kinase kinase protein, TAB1, and MAP3K7 also participate in kinase 7-interacting protein 2, TAB-2, the signal transduction induced by TGF-beta activated kinase 1/MAP3K7 TNFSF11/RANKL through the activation of the binding protein 2 receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the Target/Specificity development and function of osteoclasts. TAB2; TAB2 antibody is human specific. Recent experiments have shown that TAB2 and TAB2 antibody is predicted not to cross-react with other TAB proteins. the related protein TAB3 constitutitvely interact with the autophagy mediator Beclin-1; Reconstitution & Storage upon induction of autophagy, these proteins TAB2 antibody can be stored at 4℃ for dissociate from Beclin-1 and bind TAK1.
    [Show full text]
  • MAP3K7 Antibody Purified Mouse Monoclonal Antibody Catalog # Ao2028a
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 MAP3K7 Antibody Purified Mouse Monoclonal Antibody Catalog # AO2028a Specification MAP3K7 Antibody - Product Information Application WB, E Primary Accession O43318 Reactivity Human Host Mouse Clonality Monoclonal Isotype IgG2a Calculated MW 67.2kDa KDa Description The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. Immunogen Purified recombinant fragment of human MAP3K7 (AA: 471-579) expressed in E. Coli. Formulation Purified antibody in PBS with 0.05% sodium azide and 0.5% protein stabilizer MAP3K7 Antibody - Additional Information Gene ID 6885 Other Names Mitogen-activated protein kinase kinase kinase 7, 2.7.11.25, Transforming growth factor-beta-activated kinase 1, TGF-beta-activated kinase 1, MAP3K7, TAK1 Page 1/3 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Dilution WB~~1/500 - 1/2000 E~~1/10000 Storage Maintain refrigerated at 2-8°C for up to 6 months.
    [Show full text]
  • The Human Gene Connectome As a Map of Short Cuts for Morbid Allele Discovery
    The human gene connectome as a map of short cuts for morbid allele discovery Yuval Itana,1, Shen-Ying Zhanga,b, Guillaume Vogta,b, Avinash Abhyankara, Melina Hermana, Patrick Nitschkec, Dror Friedd, Lluis Quintana-Murcie, Laurent Abela,b, and Jean-Laurent Casanovaa,b,f aSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065; bLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris Descartes University, Institut National de la Santé et de la Recherche Médicale U980, Necker Medical School, 75015 Paris, France; cPlateforme Bioinformatique, Université Paris Descartes, 75116 Paris, France; dDepartment of Computer Science, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; eUnit of Human Evolutionary Genetics, Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Institut Pasteur, F-75015 Paris, France; and fPediatric Immunology-Hematology Unit, Necker Hospital for Sick Children, 75015 Paris, France Edited* by Bruce Beutler, University of Texas Southwestern Medical Center, Dallas, TX, and approved February 15, 2013 (received for review October 19, 2012) High-throughput genomic data reveal thousands of gene variants to detect a single mutated gene, with the other polymorphic genes per patient, and it is often difficult to determine which of these being of less interest. This goes some way to explaining why, variants underlies disease in a given individual. However, at the despite the abundance of NGS data, the discovery of disease- population level, there may be some degree of phenotypic homo- causing alleles from such data remains somewhat limited. geneity, with alterations of specific physiological pathways under- We developed the human gene connectome (HGC) to over- come this problem.
    [Show full text]
  • Datasheet: VMA00296 Product Details
    Datasheet: VMA00296 Description: MOUSE ANTI TAB2 Specificity: TAB2 Format: Purified Product Type: PrecisionAb™ Monoclonal Isotype: IgG1 Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Product Form Purified IgG - liquid Preparation Mouse monoclonal antibody purified by affinity chromatography from ascites Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN ) Stabilisers 3 Immunogen Purified recombinant fragment of human TAB2 expressed in E. coli External Database Links UniProt: Q9NYJ8 Related reagents Entrez Gene: 23118 TAB2 Related reagents Synonyms KIAA0733, MAP3K7IP2 Specificity Mouse anti Human TAB2 antibody recognizes the TGF-beta-activated kinase 1 and MAP3K7- binding protein 2, also known as TAK1-binding protein 2, mitogen-activated protein kinase and kinase kinase 7-interacting protein 2. Page 1 of 2 Encoded by the TAB2 gene, TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK.
    [Show full text]