Clp-mediated proteolysis in Gram-positive bacteria is autoregulated by thestability of a repressor

The heat shock proteins ClpC and ClpP are subunits of an ATP-dependent prot ease of Bacillus subtilis. Under non-stressed conditions, transcription of the clpC and clpP genes is negatively regulated by CtsR, the global repress or of clp gene expression. Here, CtsR was proven to be a specific substrate of the ClpCP protease under stress conditions. Two proteins of former unkn own function, McsA and McsB, which are also encoded by the clpC operon, act as modulators of CtsR repression. McsA containing zinc finger motifs stabi lizes CtsR under non-stressed conditions. McsB, a putative kinase, can inac tivate CtsR by modification to remove the repressor from the DNA and to tar get CtsR for degradation by the ClpCP protease during stress. Thus, clp gen e expression in Gram-positive bacteria is autoregulated by a novel mechanis m of controlled proteolysis, a circuit of down-regulation by stabilization and protection of a transcription repressor, and induction by presenting th e repressor to the protease, Thereby, the ClpC ATPase, a member of the Hsp1 00 family, was identified as a positive regulator of the heat shock respons e.