Flick J S, Johnston M
Department of Genetics, Washington University Medical School, St. Louis, Missouri 63110.
Mol Cell Biol. 1991 Oct;11(10):5101-12. doi: 10.1128/mcb.11.10.5101-5112.1991.
Growth of the yeast Saccharomyces cerevisiae on glucose leads to repression of transcription of many genes required for alternative carbohydrate metabolism. The GRR1 gene appears to be of central importance to the glucose repression mechanism, because mutations in GRR1 result in a pleiotropic loss of glucose repression (R. Bailey and A. Woodword, Mol. Gen. Genet. 193:507-512, 1984). We have isolated the GRR1 gene and determined that null mutants are viable and display a number of growth defects in addition to the loss of glucose repression. Surprisingly, grr1 mutations convert SUC2, normally a glucose-repressed gene, into a glucose-induced gene. GRR1 encodes a protein of 1,151 amino acids that is expressed constitutively at low levels in yeast cells. GRR1 protein contains 12 tandem repeats of a sequence similar to leucine-rich motifs found in other proteins that may mediate protein-protein interactions. Indeed, cell fractionation studies are consistent with this view, suggesting that GRR1 protein is tightly associated with a particulate protein fraction in yeast extracts. The combined genetic and molecular data are consistent with the idea that GRR1 protein is a primary response element in the glucose repression pathway and is required for the generation or interpretation of the signal that induces glucose repression.
酿酒酵母在葡萄糖上生长会导致许多参与替代碳水化合物代谢所需基因的转录受到抑制。GRR1基因似乎在葡萄糖抑制机制中至关重要,因为GRR1基因突变会导致葡萄糖抑制作用多效性丧失(R. 贝利和A. 伍德沃德,《分子与普通遗传学》193:507 - 512,1984)。我们已经分离出GRR1基因,并确定其缺失突变体是可行的,除了丧失葡萄糖抑制作用外,还表现出许多生长缺陷。令人惊讶的是,grr1突变将通常受葡萄糖抑制的SUC2基因转变为葡萄糖诱导基因。GRR1编码一种由1151个氨基酸组成的蛋白质,在酵母细胞中以低水平持续表达。GRR1蛋白包含12个串联重复序列,其序列与在其他可能介导蛋白质 - 蛋白质相互作用的蛋白质中发现的富含亮氨酸基序相似。实际上,细胞分级分离研究与这一观点一致,表明GRR1蛋白与酵母提取物中的颗粒状蛋白质部分紧密相关。综合的遗传和分子数据与GRR1蛋白是葡萄糖抑制途径中的主要反应元件这一观点一致,并且是诱导葡萄糖抑制的信号产生或解读所必需的。