Raivio T L, Popkin D L, Silhavy T J
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
J Bacteriol. 1999 Sep;181(17):5263-72. doi: 10.1128/JB.181.17.5263-5272.1999.
In Escherichia coli, the Cpx two-component regulatory system activates expression of protein folding and degrading factors in response to misfolded proteins in the bacterial envelope (inner membrane, periplasm, and outer membrane). It is comprised of the histidine kinase CpxA and the response regulator CpxR. This response plays a role in protection from stresses, such as elevated pH, as well as in the biogenesis of virulence factors. Here, we show that the Cpx periplasmic stress response is subject to amplification and repression through positive and negative autofeedback mechanisms. Western blot and operon fusion analyses demonstrated that the cpxRA operon is autoactivated. Conditions that lead to elevated levels of phosphorylated CpxR cause a concomitant increase in transcription of cpxRA. Conversely, overproduction of CpxP, a small, Cpx-regulated protein of previously unknown function, represses the regulon and can block activation of the pathway. This repression is dependent on an intact CpxA sensing domain. The ability to autoactivate and then subsequently repress allows for a temporary amplification of the Cpx response that may be important in rescuing cells from transitory stresses and cueing the appropriately timed elaboration of virulence factors.
在大肠杆菌中，Cpx双组分调节系统会响应细菌包膜（内膜、周质和外膜）中错误折叠的蛋白质，激活蛋白质折叠和降解因子的表达。它由组氨酸激酶CpxA和响应调节因子CpxR组成。这种反应在抵御诸如高pH等应激以及毒力因子的生物合成中发挥作用。在此，我们表明Cpx周质应激反应通过正、负自反馈机制受到放大和抑制。蛋白质印迹和操纵子融合分析表明cpxRA操纵子是自激活的。导致磷酸化CpxR水平升高的条件会使cpxRA的转录随之增加。相反，CpxP（一种功能未知的、受Cpx调节的小蛋白）的过量表达会抑制该调节子，并能阻断该途径的激活。这种抑制依赖于完整的CpxA传感结构域。自激活然后随后抑制的能力允许Cpx反应的暂时放大，这在将细胞从短暂应激中拯救出来以及提示毒力因子适时精细表达方面可能很重要。
