Chromosomal location of the human tumor necrosis factor receptor genes

Baker, Elizabeth; Chen, L Z; Smith, Christina; Callen, D F; Goodwin, Raymond G.; Sutherland, G R

doi:10.1159/000133127

Cited by 37 publications

(24 citation statements)

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“…In this sense, a single-gene rodent mutation (diabetes) and a quantitative trait locus (dietary obese 1) mapped to the midportion of mouse chromosome 4 have been related to obesity and/or insulin levels. Synteny relationships place their putative human homologs on 1p31 and on 1p35 through p31, respectively, which are very close to the TNFR2 gene location (on chromosome 1p36.2) (36)(37)(38). In this respect, our findings agree with those of Chagnon et al in the Quebec Family Study (39).…”

Section: Fernández-real and Associatessupporting

confidence: 90%

Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients.

Fernández‐Real¹,

Vendrell²,

Ricart³

et al. 2000

Diabetes Care

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Abbreviations: EASIA, enzyme-amplified sensitivity immunoassay; FSIVGTT, frequently sampled intravenous glucose tolerance test; PCR, polymerase chain reaction; sTNFR2, soluble fraction of tumor necrosis factor-␣ receptor; TNF-␣, tumor necrosis factor-␣; TNFR1, tumor necrosis factor-␣ receptor 1; TNFR2, tumor necrosis factor-␣ receptor 2; UTR, untranslated region; WHR, waist-to-hip ratio.A OBJECTIVE -Mice lacking the tumor necrosis factor-␣ receptor 2 (TNFR2) gene fed a highfat diet gain less weight and display reduced leptin and insulin levels. In humans, plasma levels of the soluble fraction of TNFR2 (sTNFR2) circulate in proportion to the degree of insulin resistance. The purpose of this study was to evaluate a polymorphism in the 3Ј untranslated region of the TNFR2 gene on chromosome 1 in relation to BMI, leptin levels, and insulin resistance.RESEARCH DESIGN AND METHODS -Using single-strand conformation polymorphism, the polymorphism was analyzed in 107 nondiabetic subjects (60 women, 47 men) and in 110 consecutive patients with type 2 diabetes (79 women, 31 men). In a subset of 33 healthy subjects, insulin sensitivity (minimal model analysis) was also evaluated.RESULTS -Four alleles of the TNFR2 gene were identified (A1, A2, A3, and A4). BMI and serum leptin levels were significantly increased in young carriers of the A2 allele. Plasma sTNFR2 levels were similar among the different TNFR2 gene variants. However, in subjects who did not carry the A2 allele, in young subjects, and in women, plasma sTNFR2 levels were proportional to BMI and leptin levels. In the study sample, carriers of the A2 allele (n = 18) showed significantly increased BMI, fat mass, waist-to-hip ratio, serum total and VLDL triglyceride levels, and leptin levels and had a lower insulin sensitivity index than noncarriers of the A2 variant (n = 15). The frequency of the different alleles among diabetic subjects was similar to that in the control population. However, diet-treated diabetic subjects (n = 49) who were carriers of the A2 allele exhibited significantly higher BMI and leptin levels than diet-treated noncarriers of the A2 allele.CONCLUSIONS -The presence of the A2 allele in the TNFR2 gene may predispose subjects to obesity and higher leptin levels, which may in turn predispose them to insulin resistance or vice versa. The TNFR2 gene may be involved in weight-control mechanisms.

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Section: Fernández-real and Associatessupporting

confidence: 90%

Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients.

Fernández‐Real¹,

Vendrell²,

Ricart³

et al. 2000

Diabetes Care

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“…Thus, human 4-1BB might be predicted to be on human chromosome 1 like the p80 TNF receptor [52]. The gene for CD30 is also closely linked to the p80 TNF receptor and 4-1BB, mapping to human chromosome lp36 [53].The p60 form of theTNF receptor and CD27 are also linked to each other, mapping to chromosome 1 2~1 3 [52, 541.…”

Section: G D Q L S T H T D G I S H G E R V Y V N I S H P D mentioning

confidence: 99%

Molecular cloning of a ligand for the inducible T cell gene 4‐1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor

et al. 1993

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4-1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4-1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4-1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. The gene for 4-1BB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the gene for CD30. The gene for 4-1BB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB.

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“…This molecule was first identified (4) by its ability to mediate HSV infection (HVEM) and by screening an expressed sequence tag cDNA database for sequence homology with cysteine-rich motifs of the TNFR superfamily (TR2) (5,6). The HVEM gene maps to 1p36, close to the TNFR members CD30 (7), 4-1BB (8,9), OX-40 (10), and TNFR-II (11). It encodes a 283-aa type I transmembrane protein containing a 50-residue cytoplasmic region that lacks a death domain, but, like other members of the TNFR superfamily, binds to a number of the TNFRassociated factor family of signal adaptors and activates transcription factors NF-B and AP1 (12,13).…”

mentioning

confidence: 99%

Reciprocal Expression of the TNF Family Receptor Herpes Virus Entry Mediator and Its Ligand LIGHT on Activated T Cells: LIGHT Down-Regulates Its Own Receptor

Morel¹,

Colella²,

Harrop³

et al. 2000

The Journal of Immunology

164

159

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The TNF receptor (TNFR) family plays a central role in the development of the immune response. Here we describe the reciprocal regulation of the recently identified TNFR superfamily member herpes virus entry mediator (HVEM) (TR2) and its ligand LIGHT (TL4) on T cells following activation and the mechanism of this process. T cell activation resulted in down-regulation of HVEM and up-regulation of LIGHT, which were both more pronounced in CD8+ than CD4+ T lymphocytes. The analysis of HVEM and LIGHT mRNA showed an increase in the steady state level of both mRNAs following stimulation. LIGHT, which was present in cytoplasm of resting T cells, was induced both in cytoplasm and at the cell surface. For HVEM, activation resulted in cellular redistribution, with its disappearance from cell surface. HVEM down-regulation did not rely on de novo protein synthesis, in contrast to the partial dependence of LIGHT induction. Matrix metalloproteinase inhibitors did not modify HVEM expression, but did enhance LIGHT accumulation at the cell surface. However, HVEM down-regulation was partially blocked by a neutralizing mAb to LIGHT or an HVEM-Fc fusion protein during activation. As a model, we propose that following stimulation, membrane or secreted LIGHT binds to HVEM and induces receptor down-regulation. Degradation or release of LIGHT by matrix metalloproteinases then contributes to the return to baseline levels for both LIGHT and HVEM. These results reveal a self-regulating ligand/receptor system that contributes to T cell activation through the interaction of T cells with each other and probably with other cells of the immune system.

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Chromosomal location of the human tumor necrosis factor receptor genes

Abstract: TNFR1 and TNFR2, the genes encoding the two forms of the human tumor necrosis factor receptor, were localized to normal human chromosomes by in situ hybridization and Southern blot analysis of a series of human × mouse hybrid cell lines. TNFR1 maps to 12p13 and TNFR2 maps to 1p36.

Cited by 37 publications

References 0 publications

Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients.

Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients.

Molecular cloning of a ligand for the inducible T cell gene 4‐1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor

Reciprocal Expression of the TNF Family Receptor Herpes Virus Entry Mediator and Its Ligand LIGHT on Activated T Cells: LIGHT Down-Regulates Its Own Receptor

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