Regulated Proteolysis in Bacterial Cell Cycle and Development

When: Tuesday, September 18, 2012 at 4:00 pm
Where: DA 114
Speaker: Peter Chien
Organization: U Mass Amherst
Sponsor: CIRCS

Protein degradation ensures the complete and immediate removal of undesired proteins; however, because proteolysis is irreversible, target selection must be carefully regulated.  The essential AAA+ protease ClpXP is intimately involved in the asymmetric cell division and cell cycle of the bacteria Caulobacter crescentus.   Recently, we have used a proteomic-based approach to trap novel substrates of the Caulobacter ClpP associated proteases.    We identified candidates involved in every aspect of cell maintenance and growth, illustrating instances of substrate conservation between bacterial species and employing biochemical observations to clarify rules governing substrate recognition.   In particular, we find that DNA replication is dependent on ClpXP on several levels.  Using biochemical and cell biological studies, we show that proteins responsible for initiation, elongation, and nucleotide metabolism are subject to regulated proteolysis.  Interestingly, our work also points to an unexpected role for ClpXP in generating isoforms of the DNA polymerase clamp loader complex through partial proteolysis.  Together our results highlight the importance of regulated protein degradation during the bacterial cell cycle and propose a novel mechanism of ClpXP in generating functional diversity of essential replication factors.

Host: Professor Mark Williams