| p53 and tumor necrosis factor alpha regulate the expression of a mitochondrial chloride channel protein. | |
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MedLine Citation:
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PMID: 10593946 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A novel chloride intracellular channel (CLIC) gene, clone mc3s5/mtCLIC, has been identified from differential display analysis of differentiating mouse keratinocytes from p53+/+ and p53-/- mice. The 4.2-kilobase pair cDNA contains an open reading frame of 762 base pairs encoding a 253-amino acid protein with two putative transmembrane domains. mc3s5/mtCLIC protein shares extensive homology with a family of intracellular organelle chloride channels but is the first shown to be differentially regulated. mc3s5/mtCLIC mRNA is expressed to the greatest extent in vivo in heart, lung, liver, kidney, and skin, with reduced levels in some organs from p53-/- mice. mc3s5/mtCLIC mRNA and protein are higher in p53+/+ compared with p53-/- basal keratinocytes in culture, and both increase in differentiating keratinocytes independent of genotype. Overexpression of p53 in keratinocytes induces mc3s5/mtCLIC mRNA and protein. Exogenous human recombinant tumor necrosis factor alpha also up-regulates mc3s5/mtCLIC mRNA and protein in keratinocytes. Subcellular fractionation of keratinocytes indicates that both the green fluorescent protein-mc3s5 fusion protein and the endogenous mc3s5/mtCLIC are localized to the cytoplasm and mitochondria. Similarly, mc3s5/mtCLIC was localized to mitochondria and cytoplasmic fractions of rat liver homogenates. Furthermore, mc3s5/mtCLIC colocalized with cytochrome oxidase in keratinocyte mitochondria by immunofluorescence and was also detected in the cytoplasmic compartment. Sucrose gradient-purified mitochondria from rat liver confirmed this mitochondrial localization. This represents the first report of localization of a CLIC type chloride channel in mitochondria and the first indication that expression of an organellular chloride channel can be regulated by p53 and tumor necrosis factor alpha. |
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Authors:
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E Fernández-Salas; M Sagar; C Cheng; S H Yuspa; W C Weinberg |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 274 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1999 Dec |
Date Detail:
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Created Date: 2000-01-27 Completed Date: 2000-01-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 36488-97 Citation Subset: IM |
Affiliation:
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Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. esterf@nih.gov |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AF102578 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Base Sequence Cells, Cultured Chloride Channels / biosynthesis, genetics* Cloning, Molecular Gene Expression Regulation* Genes, p53 Humans Keratinocytes / metabolism*, ultrastructure Mice Mitochondria / genetics*, metabolism* Molecular Sequence Data RNA, Messenger / analysis, genetics Rats Sequence Alignment Tumor Necrosis Factor-alpha / genetics*, metabolism Tumor Suppressor Protein p53 / genetics*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Chloride Channels; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 0/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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