Danese P N, Silhavy T J
Department of Molecular Biology, Princeton University, New Jersey 08544, USA.
Genes Dev. 1997 May 1;11(9):1183-93. doi: 10.1101/gad.11.9.1183.
In Escherichia coli, the heat shock-inducible sigma-factor sigma(E) and the Cpx two-component signal transduction system are both attuned to extracytoplasmic stimuli. For example, sigma(E) activity rises in response to the overproduction of various outer-membrane proteins. Similarly, the activity of the Cpx signal transduction pathway, which consists of an inner-membrane sensor (CpxA) and a cognate response regulator (CpxR), is stimulated by overproduction of the outer-membrane lipoprotein, NlpE. In response to these extracytoplasmic stimuli, sigma(E) and CpxA/CpxR stimulate the transcription of degP, which encodes a periplasmic protease. This suggests that CpxA/CpxR and sigma(E) both mediate protein turnover within the bacterial envelope. Here, we show that CpxA/CpxR and sigma(E) also control the synthesis of periplasmic enzymes that can facilitate protein-folding reactions. Specifically, sigma(E) controls transcription of fkpA, which specifies a periplasmic peptidyl-prolyl cis/trans isomerase. Similarly, the Cpx system controls transcription of the dsbA locus, which encodes a periplasmic enzyme required for efficient disulfide bond formation in several extracytoplasmic proteins. Taken together, these results indicate that sigma(E) and CpxA/CpxR are involved in regulating both protein-turnover and protein-folding activities within the bacterial envelope.
在大肠杆菌中，热休克诱导型σ因子σ（E）和Cpx双组分信号转导系统均能适应胞外刺激。例如，σ（E）的活性会因各种外膜蛋白的过量产生而升高。同样，由内膜传感器（CpxA）和同源应答调节因子（CpxR）组成的Cpx信号转导途径的活性，会受到外膜脂蛋白NlpE过量产生的刺激。作为对这些胞外刺激的响应，σ（E）和CpxA/CpxR会刺激degP的转录，degP编码一种周质蛋白酶。这表明CpxA/CpxR和σ（E）都介导细菌包膜内的蛋白质周转。在此，我们表明CpxA/CpxR和σ（E）还控制可促进蛋白质折叠反应的周质酶的合成。具体而言，σ（E）控制fkpA的转录，fkpA编码一种周质肽基脯氨酰顺反异构酶。同样，Cpx系统控制dsbA基因座的转录，dsbA基因座编码几种胞外蛋白质中高效形成二硫键所需的一种周质酶。综上所述，这些结果表明σ（E）和CpxA/CpxR参与调节细菌包膜内的蛋白质周转和蛋白质折叠活性。
