Laine B, Eeckhoute J, Suaud L, Briche I, Furuta H, Bell G I, Formstecher P
Unité 459 INSERM, Laboratoire de Biologie Cellulaire, Université H. Warembourg, Lille, France.
FEBS Lett. 2000 Aug 11;479(1-2):41-5. doi: 10.1016/s0014-5793(00)01864-0.
Mutations in the hepatocyte nuclear factor 4alpha (HNF-4alpha) 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-4alpha functions. Since pancreatic beta-cell dysfunction is a feature of MODY1 patients, we compared the functional properties of the R154X mutant in insulin-secreting pancreatic beta-cells and non-beta-cells. The R154X mutation did not affect nuclear localisation in beta-cells and non-beta-cells. However, it did lead to a greater impairment of HNF-4a function in beta-cells compared to non-beta-cells, including a complete loss of transactivation activity and a dominant-negative behaviour. .
肝细胞核因子4α（HNF-4α）基因的突变与一种青年发病的成年型糖尿病（MODY1）相关。R154X突变产生一种缺乏正常HNF-4α功能所需E结构域的蛋白质。由于胰腺β细胞功能障碍是MODY1患者的一个特征，我们比较了R154X突变体在胰岛素分泌胰腺β细胞和非β细胞中的功能特性。R154X突变不影响β细胞和非β细胞中的核定位。然而，与非β细胞相比，它确实导致β细胞中HNF-4α功能的更大损害，包括转录激活活性的完全丧失和显性负性作用。
