Targeted sigma factor turnover inserts negative control into a positive feedback loop.

Since their classification as members of the sigma(70) superfamily, Group IV alternative sigma factors have been found to control gene expression in response to diverse environmental or stress signals. Activity of the Streptomyces coelicolor Group IV family member, sigma(R) (SigR), is increased by changes in the oxidation-reduction state of cytoplasmic disulphide bonds. Once released by its cognate anti-sigma factor RsrA, sigma(R) activates expression of gene products that help cells reduce cytoplasmic disulphide bonds. In this issue of Molecular Microbiology, Kim and co-workers provide new insights into positive and negative control of sigma(R) activity. The authors show that a transcript derived from the inducible sigma(R)-dependent sigRrsrA p2 promoter operon encodes a sigma(R) protein of a higher molecular weight (termed sigma(R')) than is found in uninduced cells. One major difference between sigma(R') and the smaller sigma(R) protein found in uninduced cells is the rapid proteolysis of sigma(R') by the ClpP1/P2 protease system. The genes for the ClpP1/ClpP2 protease subunits are themselves members of the sigma(R) regulon. The newly identified positive (sigma(R') synthesis) and negative control (selective sigma(R') turnover) aspects of this circuit are either found or predicted to exist in other related Group IV sigma factor family members.