Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the Pap1transcription factor.

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

doi:10.1371/journal.pone.0050796

Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the Pap1transcription factor.

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

Biomolecular Sciences

10 Citations (Scopus)

627 Downloads (Pure)

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 language	English
Journal	P L o S One
Volume	7
Issue number	11
Number of pages	8
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0050796
Publication status	Published - 27 Nov 2012

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Cite this

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title = "Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the Pap1transcription factor.",

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.",

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AU - Penney, Mary

AU - Samejima, Itaru

AU - Wilkinson, Caroline

AU - McInerny, Christopher

AU - Mathiassen, Søs

AU - Wallace, Mairi

AU - Toda, Takashi

AU - Hartmann-Petersen, Rasmus

AU - Gordon, Colin

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