Connolly L, De Las Penas A, Alba B M, Gross C A
Department of Biochemistry and Biophysics, University of California, San Francisco, 94143, USA.
Genes Dev. 1997 Aug 1;11(15):2012-21. doi: 10.1101/gad.11.15.2012.
The activity of the alternate sigma-factor sigmaE of Escherichia coli is induced by several stressors that lead to the extracytoplasmic accumulation of misfolded or unfolded protein. The sigmaE regulon contains several genes, including that encoding the periplasmic protease DegP, whose products are thought to be required for maintaining the integrity of the cell envelope because cells lacking sigmaE are sensitive to elevated temperature and hydrophobic agents. Selection of multicopy suppressors of the temperature-sensitive phenotype of cells lacking sigmaE revealed that overexpression of the lipoprotein NlpE restored high temperature growth to these cells. Overexpression of NlpE has been shown previously to induce DegP synthesis by activating the Cpx two-component signal transduction pathway, and suppression of the temperature-sensitive phenotype by NlpE was found to be dependent on the Cpx proteins. In addition, a constitutively active form of the CpxA sensor/kinase also fully suppressed the temperature-sensitive defect of cells lacking sigmaE. DegP was found to be necessary, but not sufficient, for suppression. Activation of the Cpx pathway has also been shown to alleviate the toxicity of several LamB mutant proteins. Together, these results reveal the existence of two partially overlapping regulatory systems involved in the response to extracytoplasmic stress in E. coli.
大肠杆菌的替代σ因子σE的活性由多种应激源诱导，这些应激源会导致错误折叠或未折叠蛋白质在细胞外质积累。σE调控子包含多个基因，包括编码周质蛋白酶DegP的基因，其产物被认为是维持细胞膜完整性所必需的，因为缺乏σE的细胞对高温和疏水剂敏感。对缺乏σE的细胞温度敏感表型的多拷贝抑制子的筛选表明，脂蛋白NlpE的过表达恢复了这些细胞在高温下的生长。先前已表明NlpE的过表达通过激活Cpx双组分信号转导途径诱导DegP合成，并且发现NlpE对温度敏感表型的抑制依赖于Cpx蛋白。此外，CpxA传感器/激酶的组成型活性形式也完全抑制了缺乏σE的细胞的温度敏感缺陷。发现DegP是抑制所必需的，但不是充分的。Cpx途径的激活也已被证明可以减轻几种LamB突变蛋白的毒性。总之，这些结果揭示了大肠杆菌中存在两个部分重叠的调节系统，参与对细胞外质应激的反应。
