Format

Send to

Choose Destination
Biochem Biophys Res Commun. 1999 Dec 9;266(1):196-202.

Structure/function studies of hepatocyte nuclear factor-1alpha, a diabetes-associated transcription factor.

Author information

1
Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.

Abstract

Mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic beta-cell dysfunction. We have examined the effects of five diabetes-associated mutations (L12H, G191D, R263C, P379fsdelCT, and L584S585fsinsTC) on HNF-1alpha function including DNA binding ability, intracellular localization, and transactivation activity. L12H, P379fsdelCT, and L584S585fsinsTC mutations were found in patients with a clinical diagnosis of MODY, while G191D and R263C mutations were identified in patients diagnosed with type 2 diabetes. These mutations had diverse effects on the functional properties of HNF-1alpha. Comparison of the functional data with clinical information suggested that transactivation activity of mutant HNF-1alpha in beta cells like MIN6 may be the primary determinants of the phenotypic differences observed among diabetic patients with HNF-1alpha mutations.

PMID:
10581189
DOI:
10.1006/bbrc.1999.1747
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center