|Title:||Molecular chaperones affect GTP cyclohydrolase I mutations in dopa-responsive dystonia||Authors:||WUH-LIANG HWU
|Issue Date:||2004||Journal Volume:||55||Journal Issue:||6||Start page/Pages:||875-878||Source:||Annals of Neurology||Abstract:||
Unstable GTP cyclohydrolase I (GCH) mutations in dopa-responsive dystonia (DRD) can exert a dominant-negative effect in the HeLa cell model, but in a batch of cells this effect could not be shown. Through differential display, we found a higher Hsc70 expression in the non-dominant-negative cells. We further demonstrated that ectopic expression of Hsp40/Hsp70 stabilized the GCH mutant G201E. Moreover, Hsp90 inhibitor geldanamycin destroyed the wild-type GCH level, and heat shock increased the synthesis of GCH protein. Therefore, the dominant-negative effect produced by unstable proteins would be susceptible to the status of molecular chaperones, which could be the modifying genes and therapeutic targets for DRD and other genetic diseases.
|ISSN:||0364-5134||DOI:||10.1002/ana.20122||SDG/Keyword:||chaperone; DOPA; geldanamycin; guanosine triphosphate cyclohydrolase I; heat shock cognate protein 70; heat shock protein 40; heat shock protein 70; heat shock protein 90; mutant protein; protein inhibitor; article; controlled study; differential display; dominant inheritance; dominant negative effect; dopa responsive dystonia; dystonia; gene expression; gene mutation; genetic disorder; heat shock; HeLa cell; human; human cell; priority journal; protein synthesis; Animals; Animals, Newborn; Benzoquinones; Blotting, Northern; Blotting, Western; Cell Line; Cricetinae; DNA Mutational Analysis; Dystonia; Embryo; Enzyme Inhibitors; Gene Expression Regulation; Glutamic Acid; Glycine; GTP Cyclohydrolase; Heat-Shock Proteins; HSP40 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Humans; Lactams, Macrocyclic; Levodopa; Molecular Chaperones; Mutation; Proteins; Quinones; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Transfection
|Appears in Collections:||醫學系|
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