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Domain Containing (domain + containing)

Distribution by Scientific Domains
Medical Sciences100%

Terms modified by Domain Containing

  • domain containing protein
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    Selected Abstracts

    Wnt signaling stabilizes the DIXDC1 protein through decreased ubiquitin-dependent degradation

    CANCER SCIENCE, Issue 3 2010
    Lei Wang
    (Cancer Sci 2010; 101: 700,706) Wnt signaling plays key roles in development, cell growth, differentiation, polarity formation, neural development, and carcinogenesis. DIX Domain Containing 1 (DIXDC1), a novel component of the Wnt pathway, was recently cloned. DIXDC1 is the human homolog of Ccd1, a positive regulator of the Wnt signaling pathway during zebrafish neural patterning. Little has been known about DIXDC1 gene expression regulation. In the present study, we showed that the DIXDC1 protein was induced upon Wnt-3a stimulation, whereas the DIXDC1 mRNA level was not significantly increased after Wnt-3a treatment. Positive DIXDC1 staining was detected in colon cancer cells and was colocalized with ,-catenin staining. However, the DIXDC1 mRNA expression decreased in human colon cancer cells compared to the matched normal colon epithelial cells. Our further investigation showed that the DIXDC1 protein was degraded through the proteasome pathway, and the activation of canonical Wnt signaling decreased the ubiquitin-dependent degradation of both the ectopic and endogenous DIXDC1 protein. In order to explore the possible mechanism of the ubiquitination of DIXDC1, we found that the phosphorylation of DIXDC1 was inhibited by Wnt-3a. Collectively, these results indicate that canonical Wnt/,-catenin pathway activation might upregulate DIXDC1 through a post-translational mechanism by inhibiting the ubiquitin-mediated degradation of the DIXDC1 protein. [source]

    Candidate genes for cannabis use disorders: findings, challenges and directions

    ADDICTION, Issue 4 2009
    Arpana Agrawal
    ABSTRACT Aim Twin studies have shown that cannabis use disorders (abuse/dependence) are highly heritable. This review aims to: (i) review existing linkage studies of cannabis use disorders and (ii) review gene association studies, to identify potential candidate genes, including those that have been tested for composite substance use disorders and (iii) to highlight challenges in the genomic study of cannabis use disorders. Methods Peer-reviewed linkage and candidate gene association studies are reviewed. Results Four linkage studies are reviewed: results from these have homed in on regions on chromosomes 1, 3, 4, 9, 14, 17 and 18, which harbor candidates of predicted biological relevance, such as monoglyceride lipase (MGLL) on chromosome 3, but also novel genes, including ELTD1[epidermal growth factor (EGF), latrophilin and seven transmembrane domain containing 1] on chromosome 1. Gene association studies are presented for (a) genes posited to have specific influences on cannabis use disorders: CNR1, CB2, FAAH, MGLL, TRPV1 and GPR55 and (b) genes from various neurotransmitter systems that are likely to exert a non-specific influence on risk of cannabis use disorders, e.g. GABRA2, DRD2 and OPRM1. Conclusions There are challenges associated with (i) understanding biological complexity underlying cannabis use disorders (including the need to study gene,gene and gene,environment interactions), (ii) using diagnostic versus quantitative phenotypes, (iii) delineating which stage of cannabis involvement (e.g. use versus misuse) genes influence and (iv) problems of sample ascertainment. [source]

    Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase-1 activation in macrophages

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2010
    Andrea J. McCoy
    Abstract Aeromonas hydrophila is a Gram-negative pathogen that causes serious infectious disease in humans. A. hydrophila induces apoptosis in infected macrophages, but the host proinflammatory responses triggered by macrophage death are largely unknown. Here, we demonstrate that the infection of mouse macrophages with A. hydrophila triggers the activation of caspase-1 and release of IL-1,. Caspase-1 activation was abrogated in macrophages deficient in Nod-like receptor family, pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), but not NLR family, CARD domain containing 4 (NLRC4). The activation of the NLRP3 inflammasome was mediated by three cytotoxins (aerolysin, hemolysin and multifunctional repeat-in-toxin) produced by A. hydrophila. Our results indicated that the NLRP3 inflammasome senses A. hydrophila infection through the action of bacterial cytotoxins. [source]

    Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD)

    HISTOPATHOLOGY, Issue 5 2008
    A Chadburn
    Aims:, Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD. Methods and results:, Double immunohistochemistry and immunohistochemistry,in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6,; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic , immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein,Barr virus negative. Conclusions:, Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre. [source]

    Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis

    INFLAMMATORY BOWEL DISEASES, Issue 2 2010
    Brita Ardesjö PhD
    Abstract Background: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. Methods: Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. Results: We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. Conclusions: Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen. Inflamm Bowel Dis 2009 [source]

    Ethanol-Responsive Genes (Crtam, Zbtb16, and Mobp) Located in the Alcohol-QTL Region of Chromosome 9 Are Associated With Alcohol Preference in Mice

    ALCOHOLISM, Issue 8 2009
    Julia Weng
    Background:, Previously, our group identified cytotoxic and regulatory T-cell molecule (Crtam), zinc finger and BTB domain containing 16 (Zbtb16), and myelin-associated oligodendrocytic basic protein (Mobp) as ethanol-responsive genes in the mouse brain by gene expression profiling. In this study, we used a genetic co-segregation analysis to assess the association of Crtam, Zbtb16, and Mobp with the alcohol preference (AP) phenotype in the alcohol-preferring C57BL/6J (B6) and alcohol avoiding DBA/2J (D2) strains of mice. Methods:, Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to confirm previous microarray analysis results that Crtam, Zbtb16, and Mobp brain mRNA levels in the B6 and D2 strains are altered by ethanol treatment. The association of the 3 genes with AP was assessed in a F2 population (n = 427) derived from the reciprocal crosses involving the B6 and D2 strains. Each F2 individual was assessed for their AP using the 2 bottle choice test and genotyped for Crtam, Zbtb16, and Mobp single nucleotide polymorphisms (SNPs) that differ between B6 and D2 mice. Results:, Semi-quantitative RT-PCR analysis confirmed that Crtam, Zbtb16, and Mobp are ethanol-responsive genes. The SNP analyses show that alleles of the 3 genes co-segregate with the AP phenotype in F2 mice, where individuals homozygous for the B6 allele have higher AP than those homozygous for the D2 allele. Also, the Crtam,Zbtb16 loci that are tightly linked and the Mobp locus act in an additive fashion in determining the relative AP phenotype. Conclusion:, Our results are consistent with the hypothesis that Crtam, Zbtb16, and Mobp may be involved in AP in mice. The nature of this association remains to be established and may reflect a direct effect of these genes or an indirect effect caused by linked genes on mouse chromosome 9. [source]

    The presence of aberrant DNA methylation in noncancerous esophageal mucosae in association with smoking history

    CANCER, Issue 15 2009
    A target for risk diagnosis, prevention of esophageal cancers
    Abstract BACKGROUND: Esophageal squamous cell carcinomas (ESCCs) tend to have multiple primary lesions, and it is believed that they arise from background mucosae with accumulation of genetic/epigenetic alterations. In this study, the objective was to elucidate the effects of smoking and drinking on the accumulation of epigenetic alterations in background mucosae. METHODS: Genes that are silenced in human ESCCs were searched for by treating 3 ESCC cell lines with the demethylating agent, 5-aza-2,-deoxycytidine and performing oligonucleotide microarrays. Methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction analysis of 60 ESCCs and their corresponding background mucosae. RESULTS: Forty-seven genes were identified as methylation-silenced in at least 1 of the 3 ESCC cell lines, and 14 of those genes (claudin 6 [CLDN6]; G protein-coupled receptor 158 [GPR158]; homeobox A9 [HOXA9]; metallothionein 1M [MT1M]; neurofilament, heavy polypeptide 200 kDa [NEFH]; plakophilin 1 [PKP1]; protein phosphatase 1, regulatory [inhibitor] subunit 14A [PPP1R14A]; pyrin domain and caspase recruitment domain containing [PYCARD]; R-spondin family, member 4 [RSPO4]; testis-specific protein, Y-encoded,like 5 [TSPYL5]; ubiquitin carboxyl-terminal esterase L1 [UCHL1]; zinc-finger protein 42 homolog [ZFP42]; zinc-finger protein interacting with K protein 1 homolog [ZIK1]; and zinc-finger and SCAN domain containing 18 [ZSCAN18]) were used as markers. In the background mucosae, methylation levels of 5 genes (HOXA9, MT1M, NEFH, RSPO4, and UCHL1) had significant correlations with smoking duration (, = .268; P = .044; , = .405; P = .002; , = .285; P = .032; , = .300; P = .024; and , = .437; P = .001, respectively). In contrast, an inverse correlation between PYCARD methylation levels and alcohol intake was observed (, = ,.334, P = .025) among individuals with the inactive aldehyde dehydrogenase 2 (ALDH2) genotype. CONCLUSIONS: The current results suggested that ESCCs developed from an epigenetic field for cancerization, which was induced by exposure to carcinogenic factors, such as tobacco smoking. The epigenetic field defect will be a novel target for risk diagnosis and prevention of ESCCs. Cancer 2009. © 2009 American Cancer Society. [source]

    OCIA domain containing 2 is highly expressed in adenocarcinoma mixed subtype with bronchioloalveolar carcinoma component and is associated with better prognosis

    CANCER SCIENCE, Issue 1 2007
    Tadashi Ishiyama
    Although lung adenocarcinoma is a major cause of cancer death worldwide, details of its molecular carcinogenesis and stepwise progression are still unclear. To characterize the sequential progression from bronchioloalveolar adenocarcinoma of the lung (BAC, in situ carcinoma) to adenocarcinoma mixed subtype with BAC component, polymerase chain reaction-based cDNA suppression subtractive hybridization (SSH) was carried out using two representative cases of BAC (non-invasive tumors) and adenocarcinoma mixed subtype with BAC (invasive tumors). Through differential screening, virtual reverse northern hybridization and quantitative real-time reverse-transcription,polymerase chain reaction (qRT-PCR) we selected five genes (TncRNA, OCIAD2, ANXA2, TMED4 and LGALS4) that were expressed at significantly higher levels in invasive adenocarcinoma mixed subtype with BAC than in BAC. After in situ hybridization and qRT-PCR analyses, we confirmed that only the OCIAD2 gene showed significantly higher expression in the tumor cells of invasive adenocarcinoma mixed subtype with BAC than in BAC (P = 0.026). We then carried out in situ hybridization of OCIAD2 in 56 adenocarcinoma mixed subtype with BAC component and assessed the correlation between OCIAD2 expression and clinicopathological features. In contrast to our expectation, the patients with OCIAD2 expression showed a better clinical outcome than those without OCIAD2 expression, and OCIAD2 expression showed an inverse correlation with lymphatic invasion, blood vessel invasion and lymph node metastasis. These results suggest that OCIAD2 begins to express at the progression from in situ to invasive carcinoma, and is associated with the favorable prognosis of adenocarcinoma mixed subtype with BAC component. (Cancer Sci 2007; 98: 50,57) [source]