title: Redox-sensitive transcriptional control by a thiol/disulphide switch in the global regulator, Spx.
abstract: The Spx protein is indispensable for survival of Bacillus subtilis under disulphide stress. Its interaction with the alpha-subunit of RNA polymerase is required for transcriptional induction of genes that function in thiol homeostasis, such as thioredoxin (trxA) and thioredoxin reductase (trxB). The N-terminal end of Spx contains a Cys-X-X-Cys (CXXC) motif, which is a likely target for redox-sensitive control. We show here that Spx directly activates trxA and -B transcription by interacting with the RNA polymerase alpha-subunit, but it does so only under an oxidized condition. The transcriptional activation by Spx requires formation of an intramolecular disulphide bond between two cysteine residues that reside in the CXXC motif. The mechanism of Spx-dependent transcriptional activation is unique in that it does not involve initial Spx-DNA interaction.
authors.affiliation: Department of Environmental & Biomolecular Systems, OGI School of Science & Engineering, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Shunji
authors.initials: S
authors.lastname: Nakano
authors.forename: Kyle N
authors.initials: KN
authors.lastname: Erwin
authors.forename: Martina
authors.initials: M
authors.lastname: Ralle
authors.forename: Peter
authors.initials: P
authors.lastname: Zuber
mesh_terms: D020816:Amino Acid Motifs; D001412:Bacillus subtilis / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; D004220:Disulfides; D013438:Sulfhydryl Compounds; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D012321:DNA-Directed RNA Polymerases; C113275:RNA polymerase alpha subunit