Sánchez-Mir Laura, Salat-Canela Clàudia, Paulo Esther, Carmona Mercè, Ayté José, Oliva Baldo, Hidalgo Elena
Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003, Barcelona, Spain.
Department of Physiology, Cardiovascular Research Institute, University of California, San Francisco, 555 Mission Bay Blvd. South, San Francisco, CA, 94158, USA.
Curr Genet. 2018 Feb;64(1):97-102. doi: 10.1007/s00294-017-0730-7. Epub 2017 Aug 10.
Stress-dependent activation of signaling cascades is often mediated by phosphorylation events, but the exact nature and role of these phosphorelays are frequently poorly understood. Here, we review which are the consequences of the stress-dependent phosphorylation of a transcription factor on gene activation. In fission yeast, the MAP kinase Sty1 is activated upon several environmental hazards and promotes cell adaptation and survival, greatly through activation of a gene program mediated by the transcription factor Atf1. Although described decades ago, the role of the phosphorylation of Atf1 by Sty1 is still a matter of debate. We present here a brief review of recent data, obtained through the characterization of several phosphorylation mutant derivatives of Atf1, demonstrating that Atf1 phosphorylation does not stabilize the factor nor stimulates its binding to DNA. Rather, it provides a structural platform of interaction with the transcriptional machinery. Based on these findings, future work will establish how this phosphorylated trans-activation domain promotes the massive gene expression shift allowing cellular adaptation to stress.
信号级联反应的应激依赖性激活通常由磷酸化事件介导，但这些磷酸化传递的确切性质和作用常常鲜为人知。在此，我们综述转录因子的应激依赖性磷酸化对基因激活有哪些影响。在裂殖酵母中，丝裂原活化蛋白激酶Sty1在多种环境危害下被激活，并通过激活由转录因子Atf1介导的基因程序，极大地促进细胞适应和存活。尽管几十年前就已被描述，但Sty1对Atf1的磷酸化作用仍存在争议。我们在此简要综述通过对Atf1的几种磷酸化突变衍生物进行表征而获得的最新数据，这些数据表明Atf1磷酸化既不会使该因子稳定，也不会刺激其与DNA的结合。相反，它提供了一个与转录机制相互作用的结构平台。基于这些发现，未来的研究将确定这种磷酸化的反式激活结构域如何促进大规模的基因表达变化，从而使细胞适应应激。
