title: Design principles of the proteolytic cascade governing the sigmaE-mediated envelope stress response in Escherichia coli: keys to graded, buffered, and rapid signal transduction.
abstract: Proteolytic cascades often transduce signals between cellular compartments, but the features of these cascades that permit efficient conversion of a biological signal into a transcriptional output are not well elucidated. sigma(E) mediates an envelope stress response in Escherichia coli, and its activity is controlled by regulated degradation of RseA, a membrane-spanning anti-sigma factor. Examination of the individual steps in this protease cascade reveals that the initial, signal-sensing cleavage step is rate-limiting; that multiple ATP-dependent proteases degrade the cytoplasmic fragment of RseA and that dissociation of sigma(E) from RseA is so slow that most free sigma(E) must be generated by the active degradation of RseA. As a consequence, the degradation rate of RseA is set by the amount of inducing signal, and insulated from the "load" on and activity of the cytoplasmic proteases. Additionally, changes in RseA degradation rate are rapidly reflected in altered sigma(E) activity. These design features are attractive as general components of signal transduction pathways governed by unstable negative regulators.
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94158, USA.
authors.forename: Rachna
authors.initials: R
authors.lastname: Chaba
authors.forename: Irina L
authors.initials: IL
authors.lastname: Grigorova
authors.forename: Julia M
authors.initials: JM
authors.lastname: Flynn
authors.forename: Tania A
authors.initials: TA
authors.lastname: Baker
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gross
mesh_terms: D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D003593:Cytoplasm / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C433802:RseA protein, E coli; D012808:Sigma Factor; D014157:Transcription Factors; C063202:sporulation-specific sigma factors; D000255:Adenosine Triphosphate; D001616:beta-Galactosidase; D010450:Endopeptidases