Institute for Biology - Microbiology, Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Berlin, Germany.
Eur J Cell Biol. 2012 Oct;91(10):789-99. doi: 10.1016/j.ejcb.2012.07.006. Epub 2012 Sep 1.
Calcineurin is an important signalling protein in a plethora of Ca(2+)-regulated cellular processes. In contrast to what is known about the function of calcineurin in various organisms, information on calcineurin substrates is still limited. Here we describe the identification and characterisation of the transcription factor activated by calcineurin (TacA) in the model organism Dictyostelium discoideum. TacA is a putative zinc-finger transcription factor orthologue of yeast Crz1. In resting unstimulated cells the protein is located in the cytosol and translocates to the nucleus in a calcineurin-dependent manner after Ca(2+)-stimulation. Nuclear export of TacA is partially dependent on GskA, the Dictyostelium orthologue of mammalian GSK3. The expression of tacA is developmentally regulated with its kinetics roughly paralleling calcineurin regulation. Silencing of tacA via RNAi leads to developmental defects and dysregulation of developmentally regulated and Ca(2+)-regulated marker genes. Additionally, TacA is involved in the stress response of D. discoideum during development in a separate pathway to the well-known stress response in Dictyostelium via STATc. Finally we provide evidence that TacA is not only an orthologue of yeast Crz1 but also functionally related to mammalian NFAT.
钙调神经磷酸酶是多种钙调节细胞过程中的一种重要信号蛋白。与人们已知的钙调神经磷酸酶在各种生物体中的功能相比，关于钙调神经磷酸酶底物的信息仍然有限。在这里，我们描述了在模式生物盘基网柄菌中被钙调神经磷酸酶激活的转录因子（TacA）的鉴定和特征。TacA 是酵母 Crz1 的一种假定锌指转录因子同源物。在静止未受刺激的细胞中，该蛋白位于细胞质中，在 Ca2+刺激后以钙调神经磷酸酶依赖的方式易位到细胞核中。TacA 的核输出部分依赖于 GskA，即哺乳动物 GSK3 的盘基网柄菌同源物。tacA 的表达具有发育调控性，其动力学大致与钙调神经磷酸酶的调控相平行。通过 RNAi 沉默 tacA 会导致发育缺陷和发育调节及 Ca2+调节标记基因的失调。此外，TacA 还参与了盘基网柄菌发育过程中的应激反应，这是一条独立于通过 STATc 已知的盘基网柄菌应激反应的途径。最后，我们提供的证据表明，TacA 不仅是酵母 Crz1 的同源物，而且在功能上与哺乳动物 NFAT 相关。
