Document Detail


p53 and tumor necrosis factor alpha regulate the expression of a mitochondrial chloride channel protein.
MedLine Citation:
PMID:  10593946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
E Fernández-Salas; M Sagar; C Cheng; S H Yuspa; W C Weinberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  274     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-27     Completed Date:  2000-01-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  36488-97     Citation Subset:  IM    
Affiliation:
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.:
GENBANK/AF102578
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MeSH Terms
Descriptor/Qualifier:
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:
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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