MODE OF ACTION OF A BACTERIAL FUNCTION INVOLVED IN CELL GROWTH CONTROL

我们一直在研究蛋白质降解在调节中的作用

We have been studying the role that protein degradation plays in regulating cell growth control, through the study of mutants defective in ATP-dependent protein degradation. E. coli lon mutants are defective in cell division regulation after DNA damage, and we have previously demonstrated that this defect is due to stabilization of a highly unstable cell division inhibitor, the product of the SulA gene. lon mutants also overproduce capsular polysaccharide, and we have developed a system for the study of the regulation of the genes necessary for capsule synthesis (cps), suing cps::lac operon fusions. We have isolated and mapped mutations in three genes which regulate capsule synthesis (rcsA, rcsB, and rcsC). All three regulatory genes have been cloned, and the protein products are being identified. Genetic experiments indicated the existence of a cascade of regulatory interactions to regulate the transcription from the cps structural genes; future work will allow the in vitro reonstruction of this regulatory cascade andidentification of the precise role of lon in this system. Studies on cells devoid of lon activity demonstrate the existence of other APT-dependent proteolysis systems in E. coli. We will develop genetic selections for mutations in these other protease genes, as well as the biochemical characterization of these activities. In addition, we have demonstrated the in vitro degradation of a natural Lon substrate, the lambda N protein. Further studies of this degradation process will allow an analysis of the characteristics of Lon proteolysis.