Positive roles for negative regulators in the mating response of yeast.
Positive roles for negative regulators in the mating response of yeast.
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DOI：
10.1038/msb.2012.18
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发表时间：
2012-06-05
影响因子：
9.9
通讯作者：
Elston, Timothy C.
中科院分区：
文献类型：
--
作者：
Houser, John R.;Ford, Eintou;Nagiec, Michal J.;Errede, Beverly;Elston, Timothy C.
所有细胞都必须检测环境的变化并作出反应，通常是通过基因表达的变化。酵母信息素途径已被广泛表征，是研究转录调控的理想系统。在这里，我们结合计算和实验的方法来研究由Ste12介导的转录调控，Ste12是信息素反应的关键转录因子。我们的数学模型能够解释多个反直觉的实验结果，并导致一些新的发现。首先，我们发现转录抑制因子Dig1和Dig2通过稳定Ste12积极影响转录。这种通过蛋白质相互作用实现的稳定产生了大量的Ste12，在信息素刺激后迅速被激活。其次，我们发现蛋白质降解遵循饱和动力学，解释了Ste12在表达量升高的突变体中半衰期长的原因。最后，我们的模型揭示了一种通过蛋白质相互作用增强复杂稳定性的强大完美适应的新机制。这种机制允许转录反应在比上游途径活动更短的时间尺度上起作用。
All cells must detect and respond to changes in their environment, often through changes in gene expression. The yeast pheromone pathway has been extensively characterized, and is an ideal system for studying transcriptional regulation. Here we combine computational and experimental approaches to study transcriptional regulation mediated by Ste12, the key transcription factor in the pheromone response. Our mathematical model is able to explain multiple counterintuitive experimental results and led to several novel findings. First, we found that the transcriptional repressors Dig1 and Dig2 positively affect transcription by stabilizing Ste12. This stabilization through protein–protein interactions creates a large pool of Ste12 that is rapidly activated following pheromone stimulation. Second, we found that protein degradation follows saturating kinetics, explaining the long half-life of Ste12 in mutants expressing elevated amounts of Ste12. Finally, our model reveals a novel mechanism for robust perfect adaptation through protein–protein interactions that enhance complex stability. This mechanism allows the transcriptional response to act on a shorter time scale than upstream pathway activity.
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影响因子：
16
作者：
Hao, Nan;Nayak, Sujata;Dohlman, Henrik G.
通讯作者：
Dohlman, Henrik G.
影响因子：
64.5
作者：
Chou, S;Huang, L;Liu, HP
通讯作者：
Liu, HP
DOI：
10.1073/pnas.86.15.5703
发表时间：
1989-08-01
影响因子：
11.1
作者：
DOLAN, JW;KIRKMAN, C;FIELDS, S
通讯作者：
FIELDS, S
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
5.3
作者：
MCCAFFREY, G;CLAY, FJ;SPRAGUE, GF
通讯作者：
SPRAGUE, GF