https://scholars.lib.ntu.edu.tw/handle/123456789/526032| Title: | Molecular chaperones affect GTP cyclohydrolase I mutations in dopa-responsive dystonia | Authors: | WUH-LIANG HWU Lu M.-Y. Hwa K.-Y. Fan S.-W. Lee Y.-M. |
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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-2542543646&doi=10.1002%2fana.20122&partnerID=40&md5=5b3985b42554022fd331b879c11c125b https://scholars.lib.ntu.edu.tw/handle/123456789/526032 |
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 [SDGs]SDG3 |
| Appears in Collections: | 醫學系 |
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