REGULATION OF ESCHERICHIA-COLI CELL-ENVELOPE PROTEINS INVOLVED IN PROTEIN-FOLDING AND DEGRADATION BY THE CPX 2-COMPONENT SYSTEM

We show that the two-component signal transduction system of Escherich ia coli, CpxA-CpxR, controls the expression of genes encoding cell env elope proteins involved in protein folding and degradation. These find ings are based on three lines of evidence. First, activation of the Cp x pathway induces 5- to 10-fold the synthesis of DsbA, required for di sulfide bond formation, and DegP, a major periplasmic protease. Second , using electrophoretic mobility shift and DNase I protection assays, we have shown that phosphorylated CpxR binds to elements upstream of t he transcription start sites of dsbA, degP, and ppiA (rotA), the latte r coding for a peptidyl-prolyl cis/trans isomerase. Third, we have dem onstrated increased in vivo transcription of all three genes, dsbA, de gP, and ppiA, when the Cpx pathway is activated. We have identified a putative CpxR consensus binding site that is found upstream of a numbe r of other E. coli genes. These findings suggest a potentially extensi ve Cpx regulon including genes transcribed by sigma(70) and sigma(E), which encode factors involved in protein folding as well as other cell ular functions.