Publication: Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young
Issued Date
2009-05-22
Resource Type
ISSN
10902104
0006291X
0006291X
Other identifier(s)
2-s2.0-64949179143
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Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.383, No.1 (2009), 68-72
Suggested Citation
Suwattanee Kooptiwut, Jatuporn Sujjitjoon, Nattachet Plengvidhya, Watip Boonyasrisawat, Nalinee Chongjaroen, Prapapron Jungtrakoon, Namoiy Semprasert, Hiroto Furuta, Kishio Nanjo, Napatawn Banchuin, Pa thai Yenchitsomanus Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young. Biochemical and Biophysical Research Communications. Vol.383, No.1 (2009), 68-72. doi:10.1016/j.bbrc.2009.03.130 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27224
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Title
Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young
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.