ETH-Zurich, Department of Biology, Institute of Biochemistry, Schafmattstrasse 18, CH-8093 Zurich, Switzerland.
Science. 2011 May 6;332(6030):732-5. doi: 10.1126/science.1198851.
Mitogen-activated protein kinase (MAPK) cascades are conserved signaling modules that control many cellular processes by integrating intra- and extracellular cues. The p38/Hog1 MAPK is transiently activated in response to osmotic stress, leading to rapid translocation into the nucleus and induction of a specific transcriptional program. When investigating the dynamic interplay between Hog1 activation and Hog1-driven gene expression, we found that Hog1 activation increases linearly with stimulus, whereas the transcriptional output is bimodal. Modeling predictions, corroborated by single-cell experiments, established that a slow stochastic transition from a repressed to an activated transcriptional state in conjunction with transient Hog1 activation generates this behavior. Together, these findings provide a molecular mechanism by which a cell can impose a transcriptional threshold in response to a linear signaling behavior.
丝裂原活化蛋白激酶（MAPK）级联是保守的信号模块，通过整合细胞内外的信号来控制许多细胞过程。p38/Hog1 MAPK 被短暂激活以响应渗透胁迫，导致其快速易位到核内并诱导特定的转录程序。在研究 Hog1 激活与 Hog1 驱动的基因表达之间的动态相互作用时，我们发现 Hog1 激活随刺激呈线性增加，而转录输出呈双峰。模型预测，单细胞实验的结果证实，与瞬时 Hog1 激活相结合的从受抑制到激活的转录状态的缓慢随机转变产生了这种行为。总之，这些发现提供了一种分子机制，通过该机制，细胞可以对线性信号行为施加转录阈值。
