Regulation by destruction: design of the σ^E envelope stress response

The signal transduction pathway governing the σ^E-dependent cell envelope stress response in Escherichia coli communicates information from the periplasm to σ^E in the cytoplasm via a regulated proteolytic cascade that results in the destruction of the membrane-bound antisigma factor, RseA, and the release of σ^E to direct transcription. Regulated proteolysis is used for signal transduction in all domains of life, and these pathways bear remarkable similarities in their architecture and the proteases involved. Work with the pathway governing the σ^E response has elucidated key design principles that ensure a rapid yet graded response that is buffered from inappropriate activation. Structural and biochemical studies of the proteases that mediate signal transduction reveal the molecular underpinnings enabling this design.