Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF) and lymphotoxin-alpha (LT-alpha) are members of a family of secreted and cell surface cytokines that participate in the regulation of immune and inflammatory responses. The cell surface form of LT-alpha is assembled during biosynthesis as a heteromeric complex with lymphotoxin-beta (LT-beta), a type II transmembrane protein that is another member of the TNF ligand family. Secreted LT-alpha is a homotrimer that binds to distinct TNF receptors of 60 and 80 kilodaltons; however, these receptors do not recognize the major cell surface LT-alpha-LT-beta complex. A receptor specific for human LT-beta was identified, which suggests that cell surface LT may have functions that are distinct from those of secreted LT-alpha.
 ...
PMID:A lymphotoxin-beta-specific receptor. 817 16

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are signal transducers for several members of the TNF receptor superfamily. We have identified a novel member of the TRAF family by degenerate oligonucleotide polymerase chain reaction amplification that contains a zinc RING finger and zinc finger motifs, a coiled-coil region, and a C-terminal "TRAF" homology domain. In vitro translated TRAF5 binds to the cytoplasmic region of the lymphotoxin-beta receptor (LT-betaR) but not to several other related receptors including CD40, both TNF receptors, Fas, and nerve growth factor receptor. TRAF5 and LT-betaR coimmunoprecipitate when overexpressed in COS7 cells. TRAF5 mRNA expression is found in all visceral organs and overlaps with LT-betaR. These features distinguish TRAF5 from the other members of the TRAF family. The transcription factor NF-kappaB is activated in HEK293 cells by overexpression of full-length TRAF5 but not a truncated form lacking the zinc binding region. Furthermore, overexpression of LT-betaR in HEK293 cells also results in activation of NF-kappaB, which is partially inhibited by the truncated TRAF5 mutant. These results show TRAF5 is functionally similar to TRAF2 in that both mediate activation NF-kappaB and implicate TRAF5 as a signal transducer for LT-betaR.
 ...
PMID:TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor. 866 99

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are signal transducers for members of the TNF receptor superfamily. We previously identified murine TRAF5 (mTRAF5) and showed that it specifically interacts with the lymphotoxin-beta receptor (LT-beta R) and activates the transcription factor NF-kappa B. Here we have cloned the human TRAF5 homologue (hTRAF5) by cross hybridization with mTRAF5 cDNA. hTRAF5 cDNA is composed of 2894 nucleotides with a 557-amino-acid open reading frame that exhibits 77.5 and 80% identity to mTRAF5 at the nucleotide and amino acid levels, respectively. Northern blot analysis revealed that hTRAF5 mRNA is expressed in all visceral organs. Western blotting revealed that hTRAF5 protein was abundantly expressed in the human follicular dentritic cell line, FDC-1, and to a much lesser degree in several tumor cell lines. Interspecific backcross mapping revealed that Traf5 is located in the distal region of mouse chromosome 1, which shares a region of homology with human chromosome 1q. Fluorescence in situ hybridization confirmed regional localization to human chromosome 1q32.
 ...
PMID:Human TNF receptor-associated factor 5 (TRAF5): cDNA cloning, expression and assignment of the TRAF5 gene to chromosome 1q32. 917 72

Tumor necrosis factor-alpha (TNFalpha), a proinflammatory cytokine, plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Biotechnology agents including a chimeric monoclonal anti-TNF antibody (infliximab), a humanized monoclonal anti-TNF antibody (CDP571), and a recombinant TNF receptor fusion protein (etanercept) have been used to inhibit TNFalpha activity. Controlled trials have demonstrated efficacy for infliximab in moderately to severely active Crohn's disease (CD) and fistulizing CD sufficient to justify recent U.S. Food and Drug Administration (FDA) approval. Additional trials have been completed in rheumatoid arthritis (RA). Similarly, preliminary controlled trials have suggested efficacy for CDP571 in active CD and RA. Larger controlled trials have demonstrated efficacy for etanercept in RA patients who have failed disease modifying antirheumatic drug (DMARD) therapy leading to FDA approval for RA. Toxicities observed with anti-TNF therapies have included formation of human antichimeric antibodies (HACA) with associated acute and delayed hypersensitivity infusion reactions, human antihuman antibodies (HAHAs), and formation of autoantibodies with rare instances of drug-induced lupus. Several cases of non-Hodgkin's lymphoma also has been described. Future studies should evaluate optimal timing and duration of anti-TNF therapy, the utility of adjuvant medical treatments during anti-TNF therapy, and evaluate long-term safety and efficacy of the various anti-TNF agents.
 ...
PMID:Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, and safety. 1070 Nov 57

Tumor necrosis factor (TNF) receptor types 1 and 2 are broadly expressed by most cell types and are activated by binding of either TNF or lymphotoxin-beta. TNF receptor-mediated immune reactions are critically important in the pathogenesis and control of a variety of infections caused by bacteria, viruses, protozoa, and fungi. This review summarizes recent findings on the role of TNF receptors in infectious diseases and discusses the divergent functions of these receptors in immune responses.
 ...
PMID:The divergent role of tumor necrosis factor receptors in infectious diseases. 1100 18

Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.
 ...
PMID:Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma. 1131 70

Chromosome 8p21-22 is a frequent site of loss of heterozygosity in many types of cancer, including hepatocellular carcinoma (HCC). Tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2/DR5), a member of tumor necrosis factor receptor family, is mapped to chromosome 8p21-22. Mutations of TRAIL-R2 have been detected in lung cancer, breast cancer, head and neck cancer, and non-Hodgkin's lymphoma. In this study, we analyzed the entire coding regions and all splicing sites of TRAIL-R2 in 40 HCCs and the death domain region in additional 60 HCCs. We could detect one point mutation in the death domain in only one HCC (1%). Our data suggest that somatic mutations of TRAIL-R2 gene do not play an important role in the carcinogenesis of HCC.
 ...
PMID:Mutation of the DR5/TRAIL receptor 2 gene is infrequent in hepatocellular carcinoma. 1217 36

Tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-beta receptor (LTbetaR) signaling both play important roles in inflammatory and immune responses through activation of NF-kappaB. Using various deficient mouse embryonic fibroblast cells, we have compared the signaling pathways leading to NF-kappaB induction in response to TNF-alpha and LTbetaR activation. We demonstrate that LTbetaR ligation induces not only RelA/p50 dimers but also RelB/p50 dimers, whereas TNF-alpha induces only RelA/p50 dimers. LTbetaR-induced binding of RelB/p50 requires processing of p100 that is mediated by IKKalpha but is independent of IKKbeta, NEMO/IKKgamma, and RelA. Moreover, we show that RelB, p50, and p100 can associate in the same complex and that TNF-alpha but not LTbeta signaling increases the association of p100 with RelB/p50 dimers in the nucleus, leading to the specific inhibition of RelB DNA binding. These results suggest that the alternative NF-kappaB pathway based on p100 processing may account not only for the activation of RelB/p52 dimers but also for that of RelB/p50 dimers and that p100 regulates the binding activity of RelB/p50 dimers via at least two distinct mechanisms depending on the signaling pathway involved.
 ...
PMID:RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. 1270 43

Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory mediator and has also the potential as a prominent biomarker of innate immunity. In this study, we identified and characterized TNF-alpha from bluefin tuna, which is an important cultured species. Two types of TNF-alpha were also cloned incidentally (TNF1 and TNF2). The open reading frame of TNF1 and TNF2 cDNA encoded 247 and 245 amino acids, respectively. The amino acid sequence identity among sea perch, red sea bream, and tiger puffer was 73, 70, 59% for TNF1 and 49, 51, 45% for TNF2, respectively. The identity between TNF1 and TNF2 amino acid sequences of the bluefin tuna was only 43%. The positions of cysteine residues, transmembrane sequence, and protease cleavage site in bluefin tuna TNFs were similar with other reported fish and mammalian TNF-alpha. In a phylogenetic analysis, TNF1 is grouped with other reported Perciformes TNF-alpha. On the other hand, TNF2 is grouped with ayu TNF and is quite distant from the fish TNF-alpha group and lymphotoxin-beta group. While TNF1 mRNA showed no significant difference in all tissues, TNF2 mRNA was expressed significantly higher in the blood than in the gill, intestine, head kidney, spleen, heart, and ovary. In peripheral blood leucocytes (PBL), expressions of TNF2 mRNA were significantly increased by stimulation with lipopolysaccharide, phytohemagglutinin, concanavalin A, pokeweed mitogen, phorbol myristate acetate in vitro, but those of TNF1 were not. Recombinant mature TNF1 and TNF2 proteins significantly enhanced phagocytic activity of PBL. Our results suggest that bluefin tuna possess two types of TNF-alpha homologue, and TNF2 is a potential biomarker for innate immunity.
 ...
PMID:Two types of tumor necrosis factor-alpha in bluefin tuna (Thunnus orientalis) genes: Molecular cloning and expression profile in response to several immunological stimulants. 1914 59

Tumor necrosis factor (TNF)-related cytokines function as key communication systems between cells of the immune system and mediate inflammation and tissue destruction. LIGHT (TNFSF14) is a key component of the communication system that controls the responses of T-Cells. LIGHT activates two cell surface receptors, the Herpesvirus Entry Mediator (HVEM) and the Lymphotoxin-beta Receptor and is inhibited by soluble decoy receptor-3. The LIGHT-HVEM pathway is an important cosignaling pathway for T-Cells, whereas LIGHT-LTbetaR modifies the functions of dendritic cells and stromal cells by creating tissue microenvironments, which promote immune responses. HVEM also binds an Ig superfamily member, B and T lymphocyte attenuator (BTLA) that inhibits T-Cell activation. Thus, HVEM serves as a molecular switch between stimulatory and inhibitory signaling. Studies in humans and experimental animal models reveal that LIGHT contributes to inflammation and pathogenesis in mucosal, hepatic, joint and vascular tissues. LIGHT is accessible to biologic-based therapeutics, which can be used to target this molecule during inflammation-driven diseases.
 ...
PMID:Targeting the LIGHT-HVEM pathway. 1976 72


1 2 Next >>