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|Title:||Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young|
Pa thai Yenchitsomanus
Faculty of Medicine, Siriraj Hospital, Mahidol University
Wakayama Medical University
Thailand National Center for Genetic Engineering and Biotechnology
|Keywords:||Biochemistry, Genetics and Molecular Biology|
|Citation:||Biochemical and Biophysical Research Communications. Vol.383, No.1 (2009), 68-72|
|Abstract:||A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1α (HNF-1α) encoding a truncated HNF-1α (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-1α proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1α could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1α 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-1α (G554fsX556) on the transactivation of its target-gene promoters would account for the β-cell dysfunction associated with the pathogenesis of MODY. © 2009 Elsevier Inc. All rights reserved.|
|Appears in Collections:||Scopus 2006-2010|
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