THE SIGMA(E) AND THE CPX SIGNAL-TRANSDUCTION SYSTEMS CONTROL THE SYNTHESIS OF PERIPLASMIC PROTEIN-FOLDING ENZYMES IN ESCHERICHIA-COLI

In Escherichia coli, the heat shock-inducible sigma-factor sigma(E) an d the Cpx two-component signal transduction system are both attuned to extracytoplasmic stimuli. For example, sigma(E) activity rises in res ponse to the overproduction of various outer-membrane proteins. Simila rly, the activity of the Cpx signal transduction pathway, which consis ts of an inner-membrane sensor (CpxA) and a cognate response regulator (CpxR), is stimulated by overproduction of the outer-membrane lipopro tein, NlpE. In response to these extracytoplasmic stimuli, sigma(E) an d CpxA/CpxR stimulate the transcription of degP, which encodes a perip lasmic protease. This suggests that CpxA/CpxR and sigma(E) both mediat e protein turnover within the bacterial envelope. Here, we show that C pxA/CpxR and sigma(E) also control the synthesis of periplasmic enzyme s that can facilitate protein-folding reactions. Specifically, sigma(E ) controls transcription of FkpA, which specifies a periplasmic peptid yl-prolyl cis/trans isomerase. Similarly, the Cpx system controls tran scription of the dsbA locus, which encodes a periplasmic enzyme requir ed for efficient disulfide bond formation in several extracytoplasmic proteins. Taken together, these results indicate that sigma(E) and Cpx A/CpxR are involved in regulating both protein-turnover and protein-fo lding activities within the bacterial envelope.