摘要

与其他细胞蛋白相比，几种关键转录因子具有异常短的半衰期。 在这里，我们探讨了主动降解在塑造多种抗生素抗性激活剂MarA如何协调其下游靶标方面的效用。 MarA控制大肠杆菌中的各种应激反应基因。 我们通过敲除通过CRISPRi靶向它的蛋白酶或通过设计MarA来保护其免于降解来改变其半衰期。 我们的实验和分析结果表明，主动降解可以影响协调速率和下游基因可以实现的最大协调。 在多基因调控的背景下，这些属性之间的权衡表明，完美的信息保真度和瞬时协调不能共存。

Several key transcription factors have unusually short half-lives compared to other cellular proteins. Here, we explore the utility of active degradation in shaping how the multiple antibiotic resistance activator MarA coordinates its downstream targets. MarA controls a variety of stress response genes in Escherichia coli. We modify its half-life either by knocking down the protease that targets it via CRISPRi or by engineering MarA to protect it from degradation. Our experimental and analytical results indicate that active degradation can impact both the rate of coordination and the maximum coordination that downstream genes can achieve. In the context of multi-gene regulation, trade-offs between these properties show that perfect information fidelity and instantaneous coordination cannot coexist.

https://www.ncbi.nlm.nih.gov/pubmed/30589845