Lane S, Zhou S, Pan T, Dai Q, Liu H
Department of Biological Chemistry, University of California, Irvine, California 92697-1700, USA.
Mol Cell Biol. 2001 Oct;21(19):6418-28. doi: 10.1128/MCB.21.19.6418-6428.2001.
Candida albicans undergoes a morphogenetic switch from budding yeast to hyphal growth form in response to a variety of stimuli and growth conditions. Multiple signaling pathways, including a Cph1-mediated mitogen-activated protein kinase pathway and an Efg1-mediated cyclic AMP/protein kinase A pathway, regulate the transition. Here we report the identification of a basic helix-loop-helix transcription factor of the Myc subfamily (Cph2) by its ability to promote pseudohyphal growth in Saccharomyces cerevisiae. Like sterol response element binding protein 1, Cph2 has a Tyr instead of a conserved Arg in the basic DNA binding region. Cph2 regulates hyphal development in C. albicans, as cph2/cph2 mutant strains show medium-specific impairment in hyphal development and in the induction of hypha-specific genes. However, many hypha-specific genes do not have potential Cph2 binding sites in their upstream regions. Interestingly, upstream sequences of all known hypha-specific genes are found to contain potential binding sites for Tec1, a regulator of hyphal development. Northern analysis shows that TEC1 transcription is highest in the medium in which cph2/cph2 displays a defect in hyphal development, and Cph2 is necessary for this transcriptional induction of TEC1. In vitro gel mobility shift experiments show that Cph2 directly binds to the two sterol regulatory element 1-like elements upstream of TEC1. Furthermore, the ectopic expression of TEC1 suppresses the defect of cph2/cph2 in hyphal development. Therefore, the function of Cph2 in hyphal transcription is mediated, in part, through Tec1. We further show that this function of Cph2 is independent of the Cph1- and Efg1-mediated pathways.
白色念珠菌会根据多种刺激和生长条件经历从出芽酵母到菌丝生长形式的形态发生转变。多种信号通路，包括由Cph1介导的丝裂原活化蛋白激酶通路和由Efg1介导的环磷酸腺苷/蛋白激酶A通路，调节这一转变。在此我们报告通过其促进酿酒酵母假菌丝生长的能力鉴定出一种Myc亚家族的碱性螺旋-环-螺旋转录因子（Cph2）。与固醇反应元件结合蛋白1一样，Cph2在碱性DNA结合区域有一个酪氨酸而非保守的精氨酸。Cph2调节白色念珠菌中的菌丝发育，因为cph2/cph2突变株在菌丝发育和菌丝特异性基因的诱导方面表现出培养基特异性损伤。然而，许多菌丝特异性基因在其上游区域没有潜在的Cph2结合位点。有趣的是，所有已知菌丝特异性基因的上游序列都含有菌丝发育调节因子Tec1的潜在结合位点。Northern分析表明，在cph2/cph2表现出菌丝发育缺陷的培养基中，TEC1转录最高，并且Cph2是TEC1这种转录诱导所必需的。体外凝胶迁移率变动实验表明，Cph2直接结合到TEC1上游的两个固醇调节元件1样元件上。此外，TEC1的异位表达抑制了cph2/cph2在菌丝发育方面的缺陷。因此，Cph2在菌丝转录中的功能部分是通过Tec1介导的。我们进一步表明，Cph2的这种功能独立于Cph1和Efg1介导的通路。
