A novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe.

2.50
Hdl Handle:
http://hdl.handle.net/10541/74836
Title:
A novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe.
Authors:
Thornton, Gemma; Wilkinson, Caroline R M; Toone, W Mark; Jones, Nic
Abstract:
In this study, we show that a mutation isolated during a screen for determinants of chemosensitivity in S. pombe results in loss of function of a previously uncharacterized protein kinase now named Hal4. Hal4 shares sequence homology to Hal4 and Hal5 in S. cerevisiae, and previous evidence indicates that these kinases positively regulate the major potassium transporter Trk1,2 and thereby maintain the plasma membrane potential. Disruption of this ion homeostasis pathway results in a hyperpolarized membrane and a concomitant increased sensitivity to cations. We demonstrate that a mutation in hal4+ results in hyperpolarization of the plasma membrane. In addition to the original selection agent, the hal4-1 mutant is sensitive to a variety of chemotherapeutic agents and stress-inducing compounds. Furthermore, this wider chemosensitive phenotype is also displayed by corresponding mutants in S. cerevisiae, and in a trk1deltatrk2delta double deletion mutant in S. pombe. We propose that this pathway and its role in regulating the plasma membrane potential may act as a pleiotropic determinant of sensitivity to chemotherapeutic agents.
Affiliation:
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.
Citation:
A novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe. 2005, 10 (10):941-51 Genes Cells
Journal:
Genes to Cells
Issue Date:
Oct-2005
URI:
http://hdl.handle.net/10541/74836
DOI:
10.1111/j.1365-2443.2005.00891.x
PubMed ID:
16164595
Type:
Article
Language:
en
ISSN:
1356-9597
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorThornton, Gemma-
dc.contributor.authorWilkinson, Caroline R M-
dc.contributor.authorToone, W Mark-
dc.contributor.authorJones, Nic-
dc.date.accessioned2009-07-21T16:58:05Z-
dc.date.available2009-07-21T16:58:05Z-
dc.date.issued2005-10-
dc.identifier.citationA novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe. 2005, 10 (10):941-51 Genes Cellsen
dc.identifier.issn1356-9597-
dc.identifier.pmid16164595-
dc.identifier.doi10.1111/j.1365-2443.2005.00891.x-
dc.identifier.urihttp://hdl.handle.net/10541/74836-
dc.description.abstractIn this study, we show that a mutation isolated during a screen for determinants of chemosensitivity in S. pombe results in loss of function of a previously uncharacterized protein kinase now named Hal4. Hal4 shares sequence homology to Hal4 and Hal5 in S. cerevisiae, and previous evidence indicates that these kinases positively regulate the major potassium transporter Trk1,2 and thereby maintain the plasma membrane potential. Disruption of this ion homeostasis pathway results in a hyperpolarized membrane and a concomitant increased sensitivity to cations. We demonstrate that a mutation in hal4+ results in hyperpolarization of the plasma membrane. In addition to the original selection agent, the hal4-1 mutant is sensitive to a variety of chemotherapeutic agents and stress-inducing compounds. Furthermore, this wider chemosensitive phenotype is also displayed by corresponding mutants in S. cerevisiae, and in a trk1deltatrk2delta double deletion mutant in S. pombe. We propose that this pathway and its role in regulating the plasma membrane potential may act as a pleiotropic determinant of sensitivity to chemotherapeutic agents.en
dc.language.isoenen
dc.subject.meshCation Transport Proteins-
dc.subject.meshCations-
dc.subject.meshCell Membrane-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshDrug Resistance, Multiple, Fungal-
dc.subject.meshEscherichia coli-
dc.subject.meshGene Expression Regulation, Fungal-
dc.subject.meshGenes, Fungal-
dc.subject.meshMembrane Potentials-
dc.subject.meshMutation-
dc.subject.meshPotassium Chloride-
dc.subject.meshProtein Kinases-
dc.subject.meshSaccharomyces cerevisiae Proteins-
dc.subject.meshSchizosaccharomyces-
dc.subject.meshSchizosaccharomyces pombe Proteins-
dc.subject.meshSequence Homology-
dc.titleA novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.en
dc.identifier.journalGenes to Cellsen
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