title: RseA, the SigE specific anti-sigma factor of Mycobacterium tuberculosis, is inactivated by phosphorylation-dependent ClpC1P2 proteolysis.
abstract: Central to the response of Mycobacterium tuberculosis to environmental stress is the regulation of genes under the control of alternative sigma factors. Sigma E of M. tuberculosis plays an important role in the intracellular life of the bacterium and regulates several genes which are important for maintaining the integrity of the cell envelope stress. This makes it important to understand how SigE is activated under stress. Here we elucidate the mechanisms regulating interaction of SigE with its cognate anti-sigma factor RseA. Cysteines 70 and 73 are required for redox-dependent interaction of RseA with SigE. Under surface stress, PknB-dependent phosphorylation of RseA on T39 is required for its cleavage by ClpC1P2 thereby activating the SigE regulon. Rv2745c (MSMEG_2694), a transcriptional regulator, activates the clp regulon in response to vancomycin-induced stress. Taken together with the previous report that Rv2745c is activated by SigE, our study uncovers a positive feedback loop that activates the sigE regulon under envelope stress.
authors.affiliation: Department of Chemistry, 93/1 Acharya Prafulla Chandra Road, Kolkata 700009, India.
authors.forename: Subhasis
authors.initials: S
authors.lastname: Barik
authors.forename: Kamakshi
authors.initials: K
authors.lastname: Sureka
authors.forename: Partha
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Joyoti
authors.initials: J
authors.lastname: Basu
authors.forename: Manikuntala
authors.initials: M
authors.lastname: Kundu
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003545:Cysteine / Q000502:physiology; D049071:Endopeptidase Clp / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018085:Regulon; D012808:Sigma Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; C534073:ClpC1 protein, Mycobacterium tuberculosis; D006360:Heat-Shock Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C111259:sigE protein, Bacteria; D014640:Vancomycin; C475060:PknB protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases; D049071:Endopeptidase Clp; D003545:Cysteine