|Title:||Molecular Chaperones Affect Gtp Cyclohydrolase I Mutations in Dopa- Responsive Dystonia||Authors:||HWU, WUH-LIANG
LEE, YU- MAY
|Keywords:||GENE||Issue Date:||2004||Journal Volume:||v.55||Journal Issue:||n.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.
|Appears in Collections:||醫學系|
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