Clp-mediated proteolysis in Gram-positive bacteria is autoregulated by the stability of a repressor.
The heat shock proteins ClpC and ClpP are subunits of an ATP-dependent protease of Bacillus subtilis. Under non-stressed conditions, transcription of the clpC and clpP genes is negatively regulated by CtsR, the global repressor of clp gene expression. Here, CtsR was proven to be a specific substrate of the ClpCP protease under stress conditions. Two proteins of former unknown function, McsA and McsB, which are also encoded by the clpC operon, act as modulators of CtsR repression. McsA containing zinc finger motifs stabilizes CtsR under non-stressed conditions. McsB, a putative kinase, can inactivate CtsR by modification to remove the repressor from the DNA and to target CtsR for degradation by the ClpCP protease during stress. Thus, clp gene expression in Gram-positive bacteria is autoregulated by a novel mechanism of controlled proteolysis, a circuit of down-regulation by stabilization and protection of a transcription repressor, and induction by presenting the repressor to the protease. Thereby, the ClpC ATPase, a member of the Hsp100 family, was identified as a positive regulator of the heat shock response.
Krüger
E
E
Institut für Biochemie, Humboldt Universität, Universitätsklinikum Charité, Monbijoustrasse 2, D-10117 Berlin, Germany. elke.krueger@charite.de
Zühlke
D
D
Witt
E
E
Ludwig
H
H
Hecker
M
M
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D049071:Endopeptidase Clp; D005798:Genes, Bacterial; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009876:Operon; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; C087481:ClpC protein, Bacteria; D017931:DNA Primers; D006360:Heat-Shock Proteins; C423321:McsA protein, Bacillus subtilis; D012097:Repressor Proteins; D011494:Protein Kinases; C423322:McsB protein, Bacillus subtilis; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases