小兒科HWU, WUH-LIANGWUH-LIANGHWUHWA, KUO-YUANKUO-YUANHWALEE, YU- MAYYU- MAYLEE2008-12-292018-07-112008-12-292018-07-112004http://ntur.lib.ntu.edu.tw//handle/246246/94877Unstable 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.en-USGENEjournal article