Proteolysis and Regulation of Bacterial Cell Growth Control

Division Of Basic Sciences - Nci

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Abstract

During the past year we have been carrying out parallel projects on the regulation of the central bacterial regulator RpoS by selective and regulated proteolysis. The RpoS sigma factor mediates the general stress response in E. coli and other bacteria. It is necessary during stress and in stationary phase, but must be kept at low levels when cells are growing rapidly. RpoS is rapidly degraded in non-stressed cells, dependent upon the RssB adaptor protein and the ClpXP ATP-dependent protease. RssB binds RpoS and delivers it to the Clp protease. During stress conditions, anti-adaptor proteins, including the IraP protein, bind RssB and block it's ability to mediate RpoS degradation, IraP is made in response to phosphate starvation. In an extensive study of the recovery from phosphate starvation, we demonstrated that the cell rapidly recovers from RpoS stabilization, resuming RpoS degradation within minutes of the return of the nutrient, even though IraP levels do not change. A feedback loop was demonstrated to be important for recovery, by increasing RssB levels during the starvation period. Crl, a protein that allows RpoS to better access RNA polymerase and thus activate RpoS-dependent genes, is necessary as well for recovery. This work has been published, along with an extensive review of the RpoS stress response and the multiple levels of regulation. Additional work characterizing the IraP protein and the ways in which the RssB protein operates in other species are underway to better understand these complex regulatory mechanisms and their physiological roles in the cell.