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  1. Artikel: Identification of vitamin D receptor as a target of p63.

    Kommagani, R / Caserta, T M / Kadakia, M P

    Oncogene

    2006  Band 25, Heft 26, Seite(n) 3745–3751

    Abstract: p63, a p53 homolog has been shown to play a role in development and cancer. p63 is essential for both commitment of ectoderm to stratified epithelia and for the proliferative potential of epithelial stem cells. p63 knockout mice are born with severe ... ...

    Abstract p63, a p53 homolog has been shown to play a role in development and cancer. p63 is essential for both commitment of ectoderm to stratified epithelia and for the proliferative potential of epithelial stem cells. p63 knockout mice are born with severe development defects and lack organs of epithelial origin. In addition, p63 has also been shown to play a role in cancer development through the differential regulation of genes with tumor suppressor function and genes involved in metastasis. In order to understand the role of p63 in cancer and development, genes that are specifically regulated by p63 but not p53 were identified. In this study, we provide evidence that p63gamma specifically upregulates vitamin D Receptor (VDR). In contrast, p53 does not appear to be involved in upregulation of VDR expression. Additionally, we demonstrate that a naturally occurring p63 missense mutant, p63gamma (R279H) and p14(ARF), both act in a dominant negative manner to inhibit p63gamma-mediated upregulation of VDR. Furthermore, using chromatin immunoprecipitation assays, we demonstrated that p63 directly binds to the VDR promoter in vivo. Our findings clearly demonstrate that VDR is a direct target of p63 and suggests that p63 may play a role in cancer and differentiation through modulation of the VDR pathway.
    Mesh-Begriff(e) Bone Neoplasms/genetics ; Bone Neoplasms/pathology ; Cell Differentiation/genetics ; Chromatin Immunoprecipitation ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation ; HeLa Cells ; Humans ; Mutation, Missense ; Osteosarcoma/genetics ; Osteosarcoma/pathology ; Promoter Regions, Genetic ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Response Elements ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factors ; Tumor Cells, Cultured ; Tumor Suppressor Protein p14ARF/genetics ; Tumor Suppressor Protein p14ARF/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
    Chemische Substanzen DNA-Binding Proteins ; Receptors, Calcitriol ; TP63 protein, human ; Trans-Activators ; Transcription Factors ; Tumor Suppressor Protein p14ARF ; Tumor Suppressor Proteins
    Sprache Englisch
    Erscheinungsdatum 2006-06-22
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/sj.onc.1209412
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties.

    Caserta, T M / Smith, A N / Gultice, A D / Reedy, M A / Brown, T L

    Apoptosis : an international journal on programmed cell death

    2003  Band 8, Heft 4, Seite(n) 345–352

    Abstract: In recent years, several inhibitors that prevent caspase activation and apoptosis have emerged. At high doses, however, these inhibitors can have nonspecific effects and/or become cytotoxic. In this study, we determined the effectiveness of broad ... ...

    Abstract In recent years, several inhibitors that prevent caspase activation and apoptosis have emerged. At high doses, however, these inhibitors can have nonspecific effects and/or become cytotoxic. In this study, we determined the effectiveness of broad spectrum caspase inhibitors to prevent apoptosis. A carboxy terminal phenoxy group conjugated to the amino acids valine and aspartate (Q-VD-OPh) potently inhibited apoptosis. Q-VD-OPh was significantly more effective in preventing apoptosis than the widely used inhibitors, ZVAD-fmk and Boc-D-fmk, and was also equally effective in preventing apoptosis mediated by the three major apoptotic pathways, caspase 9/3, caspase 8/10, and caspase 12. In addition to the increased effectiveness, Q-VD-OPh was not toxic to cells even at extremely high concentrations. Our data indicate that the specificity, effectiveness, and reduced toxicity of caspase inhibitors can be significantly enhanced using carboxyterminal o-phenoxy groups and may have important uses in vivo.
    Mesh-Begriff(e) Amino Acid Chloromethyl Ketones/chemistry ; Amino Acid Chloromethyl Ketones/metabolism ; Amino Acid Chloromethyl Ketones/pharmacology ; Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Benzyl Compounds/metabolism ; Benzyl Compounds/pharmacology ; Caspase Inhibitors ; Cysteine Proteinase Inhibitors/metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; DNA Fragmentation ; Dactinomycin/metabolism ; Humans ; Hydrocarbons, Fluorinated/metabolism ; Hydrocarbons, Fluorinated/pharmacology ; Jurkat Cells ; Mice ; Nucleic Acid Synthesis Inhibitors/metabolism ; Quinolines/chemistry ; Quinolines/metabolism ; Quinolines/pharmacology ; Rats ; Thapsigargin/metabolism ; Transforming Growth Factor beta/metabolism
    Chemische Substanzen Amino Acid Chloromethyl Ketones ; Benzyl Compounds ; Boc-D-FMK ; Caspase Inhibitors ; Cysteine Proteinase Inhibitors ; Hydrocarbons, Fluorinated ; Nucleic Acid Synthesis Inhibitors ; Quinolines ; Transforming Growth Factor beta ; benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone ; quinoline-val-asp(OMe)-CH2-OPH ; Dactinomycin (1CC1JFE158) ; Thapsigargin (67526-95-8)
    Sprache Englisch
    Erscheinungsdatum 2003-06-10
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1452360-7
    ISSN 1360-8185
    ISSN 1360-8185
    DOI 10.1023/a:1024116916932
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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