WUH-LIANG HWULu M.-Y.Hwa K.-Y.Fan S.-W.Lee Y.-M.2020-12-162020-12-1620040364-5134https://www.scopus.com/inward/record.uri?eid=2-s2.0-2542543646&doi=10.1002%2fana.20122&partnerID=40&md5=5b3985b42554022fd331b879c11c125bhttps://scholars.lib.ntu.edu.tw/handle/123456789/526032Unstable 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.[SDGs]SDG3chaperone; 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; Transfectionjournal article10.1002/ana.20122151740232-s2.0-2542543646