Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82316
Title:
Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1.
Authors:
Castillo, Esther A; Vivancos, Ana P; Jones, Nic; Ayte, Jose; Hidalgo, Elena
Abstract:
In Schizosaccharomyces pombe, the transcription factor Pap1, and the mitogen-activated protein kinase Sty1 are excluded from the nucleus in a Crm1-dependent manner under non-stressed conditions. Upon oxidant treatment, both Sty1 and Pap1 concentrate into the nucleus, due to an enhanced import or an impaired export. Hba1, a protein that when overexpressed confers brefeldin A resistance, contains a Ran binding domain. The purpose of this project was to understand at the molecular level the role of Hba1 in the S. pombe oxidative stress response. Fluorescent and confocal microscopy studies demonstrate that Hba1 is located at the nucleoplasm and not at the nuclear envelope. We also demonstrate that either multiple copies or deletion of the hba1 gene induces nuclear accumulation of Pap1 and Sty1. We propose that Hba1 assists Crm1 to export some nuclear export signal-containing proteins. Pap1 nuclear accumulation is sufficient for constitutive activation of its specific antioxidant response. On the contrary, constitutive nuclear localization of Sty1 in the Deltahba1 strain does not trigger the Sty1-specific, Atf1-dependent antioxidant response in the absence of stress. We conclude that the increased multidrug resistance of strains lacking or overexpressing Hba1 is due to the accumulation of Pap1 in the nucleus under non-stressed conditions.
Affiliation:
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr Aiguader 80, 08003 Barcelona, Spain.
Citation:
Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1. 2003, 278 (42):40565-72 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
17-Oct-2003
URI:
http://hdl.handle.net/10541/82316
DOI:
10.1074/jbc.M305859200
PubMed ID:
12896976
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorCastillo, Esther A-
dc.contributor.authorVivancos, Ana P-
dc.contributor.authorJones, Nic-
dc.contributor.authorAyte, Jose-
dc.contributor.authorHidalgo, Elena-
dc.date.accessioned2009-09-23T11:50:14Z-
dc.date.available2009-09-23T11:50:14Z-
dc.date.issued2003-10-17-
dc.identifier.citationSchizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1. 2003, 278 (42):40565-72 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid12896976-
dc.identifier.doi10.1074/jbc.M305859200-
dc.identifier.urihttp://hdl.handle.net/10541/82316-
dc.description.abstractIn Schizosaccharomyces pombe, the transcription factor Pap1, and the mitogen-activated protein kinase Sty1 are excluded from the nucleus in a Crm1-dependent manner under non-stressed conditions. Upon oxidant treatment, both Sty1 and Pap1 concentrate into the nucleus, due to an enhanced import or an impaired export. Hba1, a protein that when overexpressed confers brefeldin A resistance, contains a Ran binding domain. The purpose of this project was to understand at the molecular level the role of Hba1 in the S. pombe oxidative stress response. Fluorescent and confocal microscopy studies demonstrate that Hba1 is located at the nucleoplasm and not at the nuclear envelope. We also demonstrate that either multiple copies or deletion of the hba1 gene induces nuclear accumulation of Pap1 and Sty1. We propose that Hba1 assists Crm1 to export some nuclear export signal-containing proteins. Pap1 nuclear accumulation is sufficient for constitutive activation of its specific antioxidant response. On the contrary, constitutive nuclear localization of Sty1 in the Deltahba1 strain does not trigger the Sty1-specific, Atf1-dependent antioxidant response in the absence of stress. We conclude that the increased multidrug resistance of strains lacking or overexpressing Hba1 is due to the accumulation of Pap1 in the nucleus under non-stressed conditions.en
dc.language.isoenen
dc.subject.meshAntibiotics, Antifungal-
dc.subject.meshAntioxidants-
dc.subject.meshBasic-Leucine Zipper Transcription Factors-
dc.subject.meshBlotting, Western-
dc.subject.meshBrefeldin A-
dc.subject.meshCaffeine-
dc.subject.meshCell Division-
dc.subject.meshCell Nucleus-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshDrug Resistance, Multiple-
dc.subject.meshFungal Proteins-
dc.subject.meshGene Deletion-
dc.subject.meshGreen Fluorescent Proteins-
dc.subject.meshLuminescent Proteins-
dc.subject.meshMicroscopy, Confocal-
dc.subject.meshMitogen-Activated Protein Kinases-
dc.subject.meshModels, Genetic-
dc.subject.meshNuclear Proteins-
dc.subject.meshOxidative Stress-
dc.subject.meshPhenotype-
dc.subject.meshPlasmids-
dc.subject.meshProtein Structure, Tertiary-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshRNA-
dc.subject.meshSchizosaccharomyces-
dc.subject.meshSchizosaccharomyces pombe Proteins-
dc.subject.meshTime Factors-
dc.titleSchizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1.en
dc.typeArticleen
dc.contributor.departmentDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr Aiguader 80, 08003 Barcelona, Spain.en
dc.identifier.journalThe Journal of Biological Chemistryen

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