GTP Cyclohydrolase I 突變及Splicing之分子結構機轉(2/3)
Date Issued
2003
Date
2003
Author(s)
胡務亮
DOI
912314B002147
Abstract
GTP cyclohydrolase I regulates the level of tetrahydrobiopterin and in turn the
activities of nitric oxide synthase and aromatic amino acid hydroxylases. Mutations of
the GCH gene induce human diseases including malignant hyperphenylalaninemia
(HPA) and dopa-responsive dystonia (DRD). DRD is often caused by dominant GCH
mutations with residual GCH activities up to 15% of normal. GCH protein is a
multimeric protein composed of 10 identical subunits, and we have demonstrated that
both some dominant GCH mutations and the type II cDNA exerted a
dominant-negative effect toward the wild-type GCH protein. In this study, we
demonstrated the expression of wild type GCH protein (by transfecting BHK cells)
increased after heat shock. The mRNA levels were not changed, but we are not able to
detect change in protein stability by pulse-chase and immunoprecipitation study.
Cotransfection of hsp40 or hsp70 could not mimic the effect of heat shock. On the
contrary, cotransfection of hsp27 greatly decreased the expression of GCH proteins.
This study suggests regulation of GCH protein expression by a complex cellular
reaction bringing up by heat shock and the heat shock proteins.
Subjects
GTP cyclohydrolase I
Alternative splicing
Dominant-negative effect
Regulation
SDGs
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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