title: Synergistic roles of HslVU and other ATP-dependent proteases in controlling in vivo turnover of sigma32 and abnormal proteins in Escherichia coli.
abstract: Production of abnormal proteins during steady-state growth induces the heat shock response by stabilizing normally unstable sigma32 (encoded by the rpoH gene) specifically required for transcription of heat shock genes. We report here that a multicopy plasmid carrying the hslVU operon encoding a novel ATP-dependent protease inhibits the heat shock response induced by production of human prourokinase (proUK) in Escherichia coli. The overproduction of HslVU (ClpQY) protease markedly reduced the stability and accumulation of proUK and thus reduced the induction of heat shock proteins. In agreement with this finding, deletion of the chromosomal hslVU genes significantly enhanced levels of proUK and sigma32 without appreciably affecting cell growth. When the deltahslVU deletion was combined with another protease mutation (lon, clpP, or ftsH/hflB), the resulting multiple mutations caused higher stabilization of proUK and sigma32, enhanced synthesis of heat shock proteins, and temperature-sensitive growth. Furthermore, overproduction of HslVU protease reduced sigma32 levels in strains that were otherwise expected to produce enhanced levels of sigma32 due either to the absence of Lon-ClpXP proteases or to the limiting levels of FtsH protease. Thus, a set of ATP-dependent proteases appear to play synergistic roles in the negative control of the heat shock response by modulating in vivo turnover of sigma32 as well as through degradation of abnormal proteins.
authors.affiliation: HSP Research Institute, Kyoto Research Park, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kanemori
authors.forename: K
authors.initials: K
authors.lastname: Nishihara
authors.forename: H
authors.initials: H
authors.lastname: Yanagi
authors.forename: T
authors.initials: T
authors.lastname: Yura
mesh_terms: D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D049071:Endopeptidase Clp; D010450:Endopeptidases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins; D017353:Gene Deletion; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D049070:Protease La; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism*; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C069774:heat-shock sigma factor 32; D010450:Endopeptidases; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli; D012697:Serine Endopeptidases; C483567:Lon protein, E coli; D049070:Protease La; D014568:Urokinase-Type Plasminogen Activator; C483573:ClpXP protease, E coli; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C067551:saruplase