Golan-Lavi Roni, Giacomelli Chiara, Fuks Garold, Zeisel Amit, Sonntag Johanna, Sinha Sanchari, Köstler Wolfgang, Wiemann Stefan, Korf Ulrike, Yarden Yosef, Domany Eytan
Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Cell Rep. 2017 Mar 28;18(13):3129-3142. doi: 10.1016/j.celrep.2017.03.014.
Protein responses to extracellular cues are governed by gene transcription, mRNA degradation and translation, and protein degradation. In order to understand how these time-dependent processes cooperate to generate dynamic responses, we analyzed the response of human mammary cells to the epidermal growth factor (EGF). Integrating time-dependent transcript and protein data into a mathematical model, we inferred for several proteins their pre-and post-stimulus translation and degradation coefficients and found that they exhibit complex, time-dependent variation. Specifically, we identified strategies of protein production and degradation acting in concert to generate rapid, transient protein bursts in response to EGF. Remarkably, for some proteins, for which the response necessitates rapidly decreased abundance, cells exhibit a transient increase in the corresponding degradation coefficient. Our model and analysis allow inference of the kinetics of mRNA translation and protein degradation, without perturbing cells, and open a way to understanding the fundamental processes governing time-dependent protein abundance profiles.
蛋白质对细胞外信号的反应受基因转录、mRNA降解与翻译以及蛋白质降解的调控。为了理解这些时间依赖性过程如何协同作用以产生动态反应，我们分析了人乳腺细胞对表皮生长因子（EGF）的反应。将时间依赖性转录本和蛋白质数据整合到一个数学模型中，我们推断出几种蛋白质在刺激前后的翻译和降解系数，发现它们呈现出复杂的、时间依赖性的变化。具体而言，我们确定了蛋白质产生和降解协同作用的策略，以响应EGF产生快速、短暂的蛋白质爆发。值得注意的是，对于一些其反应需要迅速降低丰度的蛋白质，细胞会表现出相应降解系数的短暂增加。我们的模型和分析能够在不干扰细胞的情况下推断mRNA翻译和蛋白质降解的动力学，并为理解控制时间依赖性蛋白质丰度谱的基本过程开辟了一条道路。
