Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

Penney, M., Samejima, I., Wilkinson, C.R., McInerny, C.J. , Mathiassen, S.G., Wallace, M., Toda, T., Hartmann-Petersen, R. and Gordon, C. (2012) Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor. PLoS ONE, 7(11), e50796. (doi: 10.1371/journal.pone.0050796) (PMID:23209828) (PMCID:PMC3507774)

[img]
Preview
Text
75937.pdf - Published Version
Available under License Creative Commons Attribution.

708kB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilkinson, Prof Caroline and McInerny, Dr Chris
Authors: Penney, M., Samejima, I., Wilkinson, C.R., McInerny, C.J., Mathiassen, S.G., Wallace, M., Toda, T., Hartmann-Petersen, R., and Gordon, C.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Published Online:27 November 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PLoS ONE 7(11):e50796
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record