Renicke Christian, Schuster Daniel, Usherenko Svetlana, Essen Lars-Oliver, Taxis Christof
Department of Biology/Genetics, Philipps-Universität Marburg, Karl-von-Frisch-Strasse 8, 35043 Marburg, Germany.
Chem Biol. 2013 Apr 18;20(4):619-26. doi: 10.1016/j.chembiol.2013.03.005.
Light perception is indispensable for plants to respond adequately to external cues and is linked to proteolysis of key transcriptional regulators. To provide synthetic light control of protein stability, we developed a generic photosensitive degron (psd) module combining the light-reactive LOV2 domain of Arabidopsis thaliana phot1 with the murine ornithine decarboxylase-like degradation sequence cODC1. Functionality of the psd module was demonstrated in the model organism Saccharomyces cerevisiae. Generation of conditional mutants, light regulation of cyclin-dependent kinase activity, light-based patterning of cell growth, and yeast photography exemplified its versatility. In silico modeling of psd module behavior increased understanding of its characteristics. This engineered degron module transfers the principle of light-regulated degradation to nonplant organisms. It will be highly beneficial to control protein levels in biotechnological or biomedical applications and offers the potential to render a plethora of biological processes light-switchable.
光感知对于植物充分响应外部信号至关重要,并且与关键转录调节因子的蛋白水解相关。为了实现对蛋白质稳定性的合成光控,我们开发了一种通用的光敏降解子(psd)模块,该模块将拟南芥光1的光反应性LOV2结构域与小鼠鸟氨酸脱羧酶样降解序列cODC1相结合。psd模块的功能在模式生物酿酒酵母中得到了验证。条件突变体的产生、细胞周期蛋白依赖性激酶活性的光调节、基于光的细胞生长模式以及酵母摄影都例证了其多功能性。对psd模块行为的计算机模拟增加了对其特性的理解。这种工程化的降解子模块将光调节降解的原理转移到了非植物生物中。它对于在生物技术或生物医学应用中控制蛋白质水平将非常有益,并提供了使大量生物过程可光开关的潜力。