http://repub.eur.nl/res/aut/14862/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/12806/ 1998-01-01T00:00:00Z Competence is a physiological state, distinct from sporulation and vegetative growth, that enables cells to bind and internalize transforming DNA. The transcriptional regulator ComK drives the development of competence in Bacillus subtilis. ComK is directly required for its own transcription as well as for the transcription of the genes that encode DNA transport proteins. When ComK is sequestered by binding to a complex of the proteins MecA and ClpC, the positive feedback loop leading to ComK synthesis is interrupted. The small protein ComS, produced as a result of signaling by a quorum-sensing two-component regulatory pathway, triggers the release of ComK from the complex, enabling comK transcription to occur. We show here, based on in vivo and in vitro experiments, that ComK accumulation is also regulated by proteolysis and that binding to MecA targets ComK for degradation by the ClpP protease in association with ClpC. The release of ComK from binding by MecA and ClpC, which occurs when ComS is synthesized, protects ComK from proteolysis. Following this release, the rates of MecA and ComS degradation by ClpCP are increased in our in vitro system. In this novel system, MecA serves to recruit ComK to the ClpCP protease and connects ComK degradation to the quorum-sensing signal-transduction pathway, thereby regulating a key developmental process. This is the first regulated degradation system in which a specific targeting molecule serves such a function.