Details

Autor(en) / Beteiligte

• Park, Joo‐Hong
• Lee, Ju‐Hyung
• Roe, Jung‐Hye

Titel

SigR, a hub of multilayered regulation of redox and antibiotic stress responses

Ist Teil von

• Molecular microbiology, 2019-08, Vol.112 (2), p.420-431

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2019

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Summary Signal‐specific activation of alternative sigma factors redirects RNA polymerase to induce transcription of distinct sets of genes conferring protection against the damage the signal and the related stresses incur. In Streptomyces coelicolor, σR (SigR), a member of ECF12 subfamily of Group IV sigma factors, responds to thiol‐perturbing signals such as oxidants and electrophiles, as well as to translation‐blocking antibiotics. Oxidants and electrophiles interact with and inactivate the zinc‐containing anti‐sigma factor, RsrA, via disulfide bond formation or alkylation of reactive cysteines, subsequently releasing σR for target gene induction. Translation‐blocking antibiotics induce the synthesis of σR, via the WhiB‐like transcription factor, WblC/WhiB7. Signal transduction via RsrA produces a dramatic transient response that involves positive feedback to produce more SigR as an unstable isoform σR′ and negative feedbacks to degrade σR′, and reduce oxidized RsrA that subsequently sequester σR and σR′. Antibiotic stress brings about a prolonged response by increasing stable σR levels. The third negative feedback, which occurs via IF3, lowers the translation efficiency of the sigRp1 transcript that utilizes a non‐canonical start codon. σR is a global regulator that directly activates > 100 transcription units in S. coelicolor, including genes for thiol homeostasis, protein quality control, sulfur metabolism, ribosome modulation and DNA repair. Close homologues in Actinobacteria, such as σH in Mycobacteria and Corynebacteria, show high conservation of the signal transduction pathways and target genes, thus reflecting the robustness of this type of regulation in response to redox and antibiotic stresses. σR (SigR), a member of ECF12 subfamily, responds to both redox and antibiotic stresses in Streptomyces coelicolor and some Actinobacteria. Thiol‐perturbing signals such as oxidants and electrophiles inactivate the zinc‐containing anti‐sigma factor, RsrA, releasing σR for target gene induction. This pathway involves positive feedback to produce σR′, an unstable isoform of σR. Translation‐inhibiting antibiotics enhance the synthesis of stable σR via a transcriptional activator WblC. Multiple feedback loops ensure fine control of optimal response.