Academic Journal
In silico and in vitro analyses of the pathological relevance of the R258H mutation of hepatocyte nuclear factor 4α identified in maturity‐onset diabetes of the young type 1
| العنوان: | In silico and in vitro analyses of the pathological relevance of the R258H mutation of hepatocyte nuclear factor 4α identified in maturity‐onset diabetes of the young type 1 |
|---|---|
| المؤلفون: | Kenji Sugawara, Kazuhiro Nomura, Yuko Okada, Aki Sugano, Masaaki Matsumoto, Toru Takarada, Atsuko Takeuchi, Hiroyuki Awano, Yushi Hirota, Hisahide Nishio, Yutaka Takaoka, Wataru Ogawa |
| المصدر: | Journal of Diabetes Investigation, Vol 10, Iss 3, Pp 680-684 (2019) |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Diseases of the endocrine glands. Clinical endocrinology |
| مصطلحات موضوعية: | Hepatocyte nuclear factor 4α, Insulin secretion, Maturity‐onset diabetes of the young type 1, Diseases of the endocrine glands. Clinical endocrinology, RC648-665 |
| الوصف: | Abstract Mutations of the hepatocyte nuclear factor 4α (HNF4α) gene give rise to maturity‐onset diabetes of the young type 1. Although many such mutations have been identified in affected individuals, part of these mutations has been characterized with regard to their pathological relevance. We here identified a missense mutation (c.773G>A, p.R258H) of HNF4A in a mother and daughter with early‐onset diabetes and impaired insulin secretion. In silico simulation and in vitro luciferase reporter analyses showed that the mutation impairs the stability of self‐dimerization and the transactivation activity of HNF4α. Although arginine‐258 does not appear to participate directly in dimerization, its mutation alters the electrostatic surface potential of the dimer interface. Our results thus suggest that this mutation impairs the function of HNF4α and thereby contributes to the pathogenesis of maturity‐onset diabetes of the young type 1. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2040-1124 2040-1116 |
| Relation: | https://doaj.org/toc/2040-1116; https://doaj.org/toc/2040-1124 |
| DOI: | 10.1111/jdi.12960 |
| URL الوصول: | https://doaj.org/article/70dab074f4e34bc998d9513fc7ca9a37 |
| رقم الانضمام: | edsdoj.70dab074f4e34bc998d9513fc7ca9a37 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20401124 20401116 |
|---|---|
| DOI: | 10.1111/jdi.12960 |