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Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young
- Source :
- Biochemical and Biophysical Research Communications. 383:68-72
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1alpha (HNF-1alpha) encoding a truncated HNF-1alpha (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1alpha proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1alpha could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1alpha on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1alpha (G554fsX556) on the transactivation of its target-gene promoters would account for the beta-cell dysfunction associated with the pathogenesis of MODY.
- Subjects :
- Transcriptional Activation
Pyruvate Kinase
Mutant
Biophysics
Electrophoretic Mobility Shift Assay
Biology
digestive system
Biochemistry
Maturity onset diabetes of the young
Frameshift mutation
Transactivation
medicine
Animals
Humans
Electrophoretic mobility shift assay
Hepatocyte Nuclear Factor 1-alpha
Promoter Regions, Genetic
Molecular Biology
Sequence Deletion
Glucose Transporter Type 2
Promoter
Cell Biology
Transfection
medicine.disease
Molecular biology
Rats
Hepatocyte nuclear factors
Diabetes Mellitus, Type 2
embryonic structures
HeLa Cells
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 383
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....3ae962ed60a4a7ed7b8c16cdde256c7e