A novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe.
Affiliation
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.Issue Date
2005-10
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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.Citation
A novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe. 2005, 10 (10):941-51 Genes CellsJournal
Genes to CellsDOI
10.1111/j.1365-2443.2005.00891.xPubMed ID
16164595Type
ArticleLanguage
enISSN
1356-9597ae974a485f413a2113503eed53cd6c53
10.1111/j.1365-2443.2005.00891.x
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