Functional properties of the R154X HNF‐4α protein generated by a mutation associated with maturity‐onset diabetes of the young, type 1

FEBS Letters

Furuta, H.¹  Laine, B.²  Suaud, L.²  Eeckhoute, J.²  Briche, I.²  Bell, G.I.¹  Formstecher, P.² 

[1] Howard Hughes Medical Institute, University of Chicago, 5841 South Maryland Avenue, MC1028, Chicago, IL 60637, USA;Unité 459 INSERM, Laboratoire de Biologie Cellulaire, Université H. Warembourg, 1 Place de Verdun, F 59045 Lille, France

关键词: Hepatocyte nuclear factor 4α;    Hormone nuclear receptor;    Maturity-onset diabetes of the young;    Diabetes mellitus;    Pancreatic β-cell;    HNF-;    hepatocyte nuclear factor;    MODY;    maturity-onset diabetes of the young;    EGFP;    enhanced green fluorescent protein;    apoCIII;    apolipoprotein CIII;    LPK;    liver pyruvate kinase;    EMSA;    electrophoretic mobility shift assays;    NLS;    nuclear localisation signal;   

DOI  :  10.1016/S0014-5793(00)01864-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mutations in the hepatocyte nuclear factor 4α (HNF-4α) gene are associated with one form of maturity-onset diabetes of the young (MODY1). The R154X mutation generates a protein lacking the E-domain which is required for normal HNF-4α functions. Since pancreatic β-cell dysfunction is a feature of MODY1 patients, we compared the functional properties of the R154X mutant in insulin-secreting pancreatic β-cells and non-β-cells. The R154X mutation did not affect nuclear localisation in β-cells and non-β-cells. However, it did lead to a greater impairment of HNF-4α function in β-cells compared to non-β-cells, including a complete loss of transactivation activity and a dominant-negative behaviour.

【 授权许可】

Unknown