title: Dual positive feedback regulation of protein degradation of an extra-cytoplasmic function σ factor for cell differentiation in Streptomyces coelicolor.
abstract: Here we report that in Streptomyces coelicolor, the protein stability of an ECF σ factor SigT, which is involved in the negative regulation of cell differentiation, was completely dependent on its cognate anti-σ factor RstA. The degradation of RstA caused a ClpP/SsrA-dependent degradation of SigT during cell differentiation. This was consistent with the delayed morphological development or secondary metabolism in the ΔclpP background after rstA deletion or sigT overexpression. Meanwhile, SigT negatively regulated clpP/ssrA expression by directly binding to the clpP promoter (clpPp). The SigT-clpPp interaction could be disrupted by secondary metabolites, giving rise to the stabilized SigT protein and retarded morphological development in a non-antibiotic-producing mutant. Thus a novel regulatory mechanism was revealed that the protein degradation of the ECF σ factor was initiated by the degradation of its anti-σ factor, and was accelerated in a dual positive feedback manner, through regulation by secondary metabolites, to promote rapid and irreversible development of the secondary metabolism. This ingenious cooperation of intracellular components can ensure economical and exquisite control of the ECF σ factor protein level for the proper cell differentiation in Streptomyces.
authors.affiliation: From the College of Life Sciences, Zhejiang University, Hangzhou 310058 and.
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Mao
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Shuai
authors.initials: S
authors.lastname: Luo
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Feng
authors.forename: Fang-Liang
authors.initials: FL
authors.lastname: Huang
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Li
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D049071:Endopeptidase Clp / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D009154:Mutation; D055550:Protein Stability; D059748:Proteolysis; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor; D049071:Endopeptidase Clp
keywords: Actinobacteria; Antibiotics; Protein Degradation; Secondary Metabolism; Transcription Regulation