Redox-sensitive transcriptional control by a thiol/disulphide switch in the global regulator, Spx

Mol Microbiol. 2005 Jan;55(2):498-510. doi: 10.1111/j.1365-2958.2004.04395.x.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Bacillus subtilis / genetics
  • Bacillus subtilis / growth & development
  • Bacillus subtilis / physiology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • DNA-Directed RNA Polymerases / metabolism
  • Disulfides / metabolism
  • Gene Expression Regulation, Bacterial*
  • Oxidation-Reduction
  • Oxidative Stress*
  • Sulfhydryl Compounds / metabolism
  • Thioredoxin-Disulfide Reductase / chemistry
  • Thioredoxin-Disulfide Reductase / genetics
  • Thioredoxin-Disulfide Reductase / metabolism
  • Thioredoxins / metabolism
  • Transcription, Genetic*
  • Transcriptional Activation

Substances

  • Bacterial Proteins
  • Disulfides
  • Sulfhydryl Compounds
  • Thioredoxins
  • Thioredoxin-Disulfide Reductase
  • DNA-Directed RNA Polymerases
  • RNA polymerase alpha subunit