Lempiäinen Harri, Uotila Aino, Urban Jörg, Dohnal Ilse, Ammerer Gustav, Loewith Robbie, Shore David
Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
Mol Cell. 2009 Mar 27;33(6):704-16. doi: 10.1016/j.molcel.2009.01.034.
Ribosome biogenesis drives cell growth, and the large transcriptional output underlying this process is tightly regulated. The Target of Rapamycin (TOR) kinase is part of a highly conserved signaling pathway linking nutritional and stress signals to regulation of ribosomal protein (RP) and ribosome biogenesis (Ribi) gene transcription. In Saccharomyces cerevisiae, one of the downstream effectors of TOR is Sfp1, a transcriptional activator that regulates both RP and Ribi genes. Here, we report that Sfp1 interacts directly with TOR complex 1 (TORC1) in a rapamycin-regulated manner, and that phosphorylation of Sfp1 by this kinase complex regulates its function. Sfp1, in turn, negatively regulates TORC1 phosphorylation of Sch9, another key TORC1 target that acts in parallel with Sfp1, revealing a feedback mechanism controlling the activity of these proteins. Finally, we show that the Sfp1-interacting protein Mrs6, a Rab escort protein involved in membrane trafficking, regulates both Sfp1 nuclear localization and TORC1 signaling.
核糖体生物合成驱动细胞生长，并且该过程背后大量的转录输出受到严格调控。雷帕霉素靶蛋白（TOR）激酶是一条高度保守的信号通路的一部分，该信号通路将营养和应激信号与核糖体蛋白（RP）及核糖体生物合成（Ribi）基因转录的调控联系起来。在酿酒酵母中，TOR的下游效应器之一是Sfp1，它是一种调节RP和Ribi基因的转录激活因子。在此，我们报道Sfp1以一种受雷帕霉素调节的方式直接与TOR复合物1（TORC1）相互作用，并且该激酶复合物对Sfp1的磷酸化作用调节其功能。反过来，Sfp1负向调节Sch9的TORC1磷酸化，Sch9是另一个与Sfp1平行作用的关键TORC1靶标，揭示了一种控制这些蛋白质活性的反馈机制。最后，我们表明与Sfp1相互作用的蛋白Mrs6，一种参与膜运输的Rab护送蛋白，调节Sfp1的核定位和TORC1信号传导。
