Kawai M, Nakashima A, Ueno M, Ushimaru T, Aiba K, Doi H, Uritani M
Department of Chemistry, Faculty of Science, Shizuoka University, 836 Oya, Shizuoka, 422-8529, Japan.
Curr Genet. 2001 May;39(3):166-74. doi: 10.1007/s002940100198.
A target of rapamycin (TOR) protein is a protein kinase that exerts cellular signal transduction to regulate cell growth in response to extracellular nutrient conditions. In the Schizosaccharomyces pombe genome database, there are two genes encoding TOR-related proteins, but their functions have not been analyzed. Here we report that one of the genes, referred to as tor1+, is required for sexual development induced by nitrogen starvation. Ste11 is a key transcription factor for the initiation of sexual development. The expression of ste11+ is normally regulated in tor1- cells; and overexpression of ste11+ hardly rescues the defect in fertility in tor1-. Upon nitrogen starvation, tor1+ cells promote two rounds of the cell cycle to become arrested at the G1 phase before initiation of sexual development. The tor1- cells do not promote such a cell cycle, suggesting that Tor1 is necessary for the response to nitrogen starvation. The tor1- cells show no growth or very slow growth under various stress conditions, including external high pH, high concentrations of salts or sorbitol, and high temperature. These results suggest that Tor1 is necessary for any response to a wide range of stresses. The vegetative growth of tor1- cells is inhibited by rapamycin, although tor1+ cells are resistant to the drug. The tor1- cells are hypersensitive to fluphenazine and cyclosporin A, which specifically inhibit calmodulin and calcineurin, respectively.
雷帕霉素靶蛋白（TOR）是一种蛋白激酶，可进行细胞信号转导，以响应细胞外营养状况来调节细胞生长。在粟酒裂殖酵母基因组数据库中，有两个编码TOR相关蛋白的基因，但其功能尚未得到分析。在此我们报告，其中一个基因，称为tor1+，是氮饥饿诱导的有性发育所必需的。Ste11是有性发育起始的关键转录因子。ste11+的表达在tor1-细胞中正常调节；并且ste11+的过表达几乎无法挽救tor1-细胞的育性缺陷。在氮饥饿时，tor1+细胞促进两轮细胞周期，在有性发育开始前停滞在G1期。tor1-细胞不促进这样的细胞周期，这表明Tor1对于对氮饥饿的反应是必需的。tor1-细胞在各种应激条件下，包括外部高pH、高浓度盐或山梨醇以及高温下，不生长或生长非常缓慢。这些结果表明Tor1对于对广泛应激的任何反应都是必需的。tor1-细胞的营养生长受到雷帕霉素的抑制，尽管tor1+细胞对该药物有抗性。tor1-细胞对氟奋乃静和环孢菌素A高度敏感，它们分别特异性抑制钙调蛋白和钙调神经磷酸酶。
