Herrero P, Martínez-Campa C, Moreno F
Departamento de Bioquímica y Biologia Molecular, Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, Spain.
FEBS Lett. 1998 Aug 28;434(1-2):71-6. doi: 10.1016/s0014-5793(98)00872-2.
The HXK2 gene plays an important role in glucose repression in the yeast Saccharomyces cerevisiae. Recently we have described that the HXK2 gene product, isoenzyme 2 of hexokinase, is located both in the nucleus and in the cytoplasm of S. cerevisiae cells. In this work we used deletion analysis to identify the essential part of the protein-mediating nuclear localisation. Determinations of fructose-kinase activity and immunoblot analysis using anti-Hxk2 antibodies in isolated nuclei, together with observations of the fluorescence distribution of Hxk2-GFP fusion protein in cells transformed with an HXK2::gfp mutant gene, indicated that the decapeptide KKPQARKGSM, located between amino acid residues 7 and 16 of hexokinase 2, is important for nuclear localisation of the protein. Further experimental evidence, measuring invertase activity in wild-type and mutant cells expressing a truncated version of the Hxk2 protein unable to enter the nucleus, shows that a nuclear localisation of Hxk2 is necessary for glucose repression signalling of the SUC2 gene. Furthermore, we demonstrate using gel mobility shift analysis that Hxk2 participates in DNA-protein complexes with cis-acting regulatory elements of the SUC2 gene promoter.
HXK2基因在酿酒酵母的葡萄糖阻遏中起重要作用。最近我们描述了HXK2基因产物,己糖激酶同工酶2,位于酿酒酵母细胞的细胞核和细胞质中。在这项工作中,我们使用缺失分析来确定介导核定位的蛋白质的关键部分。在分离的细胞核中测定果糖激酶活性并使用抗Hxk2抗体进行免疫印迹分析,以及观察用HXK2::gfp突变基因转化的细胞中Hxk2-GFP融合蛋白的荧光分布,表明位于己糖激酶2氨基酸残基7和16之间的十肽KKPQARKGSM对该蛋白的核定位很重要。进一步的实验证据,通过测量表达截短形式的Hxk2蛋白且无法进入细胞核的野生型和突变细胞中的转化酶活性,表明Hxk2的核定位对于SUC2基因的葡萄糖阻遏信号传导是必要的。此外,我们使用凝胶迁移率变动分析证明Hxk2参与与SUC2基因启动子的顺式作用调控元件形成的DNA-蛋白质复合物。