Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the Pap1 transcription factor

Mary Penney, Itaru Samejima, Caroline R Wilkinson, Christopher J McInerny, Søs G Mathiassen, Mairi Wallace, Takashi Toda, Rasmus Hartmann-Petersen, Colin Gordon

Research output: Contribution to journalArticlepeer-review

Abstract

Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes.
Original languageEnglish
Pages (from-to)e50796
JournalPLoS ONE
Volume7
Issue number11
DOIs
Publication statusPublished - 2012

Keywords

  • Brefeldin A
  • Caffeine
  • Drug Resistance, Multiple
  • Proteasome Endopeptidase Complex
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Staurosporine
  • Ubiquitination

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