Diethylmaleate activates the transcription factor Pap1 by covalent modification of critical cysteine residues.

2.50
Hdl Handle:
http://hdl.handle.net/10541/83564
Title:
Diethylmaleate activates the transcription factor Pap1 by covalent modification of critical cysteine residues.
Authors:
Castillo, Esther A; Ayte, Jose; Chiva, Cristina; Moldón, Alberto; Carrascal, Montse; Abián, Joaquín; Jones, Nic; Hidalgo, Elena
Abstract:
During the last decade, much has been learnt about the mechanisms by which oxidative stress is perceived by aerobic organisms. The Schizosaccharomyces pombe Pap1 protein is a transcription factor localized at the cytoplasm, which accumulates in the nucleus in response to different inducers, such as the pro-oxidant hydrogen peroxide (H2O2) or the glutathione-depleting agent diethylmaleate (DEM). As described for other H2O2 sensors, our genetic data indicates that H2O2 reversibly oxidizes two cysteine residues in Pap1 (Cys278 and Cys501). Surprisingly, our studies demonstrate that DEM generates a non-reversible modification of at least two cysteine residues located in or close to the nuclear export signal of Pap1 (Cys523 and Cys532). This modification impedes the interaction of the nuclear exporter Crm1 with the nuclear export signal located at the carboxy-terminal domain of Pap1. Mass spectrometry data suggest that DEM binds to the thiol groups of the target cysteine residues through the formation of a thioether. Here we show that DEM triggers Pap1 nuclear accumulation by a novel molecular mechanism.
Affiliation:
Cell Signalling Unit, Department de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Citation:
Diethylmaleate activates the transcription factor Pap1 by covalent modification of critical cysteine residues. 2002, 45 (1):243-54 Mol. Microbiol.
Journal:
Molecular Microbiology
Issue Date:
Jul-2002
URI:
http://hdl.handle.net/10541/83564
DOI:
10.1046/j.1365-2958.2002.03020.x
PubMed ID:
12100563
Type:
Article
Language:
en
ISSN:
0950-382X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorCastillo, Esther A-
dc.contributor.authorAyte, Jose-
dc.contributor.authorChiva, Cristina-
dc.contributor.authorMoldón, Alberto-
dc.contributor.authorCarrascal, Montse-
dc.contributor.authorAbián, Joaquín-
dc.contributor.authorJones, Nic-
dc.contributor.authorHidalgo, Elena-
dc.date.accessioned2009-10-05T14:55:38Z-
dc.date.available2009-10-05T14:55:38Z-
dc.date.issued2002-07-
dc.identifier.citationDiethylmaleate activates the transcription factor Pap1 by covalent modification of critical cysteine residues. 2002, 45 (1):243-54 Mol. Microbiol.en
dc.identifier.issn0950-382X-
dc.identifier.pmid12100563-
dc.identifier.doi10.1046/j.1365-2958.2002.03020.x-
dc.identifier.urihttp://hdl.handle.net/10541/83564-
dc.description.abstractDuring the last decade, much has been learnt about the mechanisms by which oxidative stress is perceived by aerobic organisms. The Schizosaccharomyces pombe Pap1 protein is a transcription factor localized at the cytoplasm, which accumulates in the nucleus in response to different inducers, such as the pro-oxidant hydrogen peroxide (H2O2) or the glutathione-depleting agent diethylmaleate (DEM). As described for other H2O2 sensors, our genetic data indicates that H2O2 reversibly oxidizes two cysteine residues in Pap1 (Cys278 and Cys501). Surprisingly, our studies demonstrate that DEM generates a non-reversible modification of at least two cysteine residues located in or close to the nuclear export signal of Pap1 (Cys523 and Cys532). This modification impedes the interaction of the nuclear exporter Crm1 with the nuclear export signal located at the carboxy-terminal domain of Pap1. Mass spectrometry data suggest that DEM binds to the thiol groups of the target cysteine residues through the formation of a thioether. Here we show that DEM triggers Pap1 nuclear accumulation by a novel molecular mechanism.en
dc.language.isoenen
dc.subject.meshBasic-Leucine Zipper Transcription Factors-
dc.subject.meshCell Nucleus-
dc.subject.meshCysteine-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFungal Proteins-
dc.subject.meshGene Expression Regulation, Fungal-
dc.subject.meshHydrogen Peroxide-
dc.subject.meshMaleates-
dc.subject.meshOxidative Stress-
dc.subject.meshSchizosaccharomyces-
dc.subject.meshSchizosaccharomyces pombe Proteins-
dc.subject.meshSignal Transduction-
dc.subject.meshSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization-
dc.titleDiethylmaleate activates the transcription factor Pap1 by covalent modification of critical cysteine residues.en
dc.typeArticleen
dc.contributor.departmentCell Signalling Unit, Department de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.en
dc.identifier.journalMolecular Microbiologyen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.