Molecular Chaperones Affect Gtp Cyclohydrolase I Mutations in Dopa- Responsive Dystonia
Resource
ANNALS OF NEUROLOGY v.55 n.6 pp.875-878
Journal
ANNALS OF NEUROLOGY
Journal Volume
v.55
Journal Issue
n.6
Pages
875-878
Date Issued
2004
Date
2004
Author(s)
HWU, WUH-LIANG
HWA, KUO-YUAN
LEE, YU- MAY
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.
Subjects
GENE
Type
journal article