SCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast.

2.50
Hdl Handle:
http://hdl.handle.net/10541/74822
Title:
SCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast.
Authors:
Harrison, Clare; Katayama, Satoshi; Dhut, Susheela; Chen, Dongrong; Jones, Nic; Bähler, Jürg; Toda, Takashi
Abstract:
Ubiquitin-dependent proteolysis regulates gene expression in many eukaryotic systems. Pof1 is an essential fission yeast F-box protein that is homologous to budding yeast Met30. Temperature-sensitive pof1 mutants display acute growth arrest with small cell size. Extragenic suppressor analysis identified Zip1, a bZIP (basic leucine zipper) transcription factor, as a target for Pof1. We show Zip1 is stabilized in pof1 mutants, Pof1 binds only phosphorylated forms of Zip1, and Zip1 is ubiquitylated in vivo, indicating that Zip1 is a substrate of SCF(Pof1). Genome-wide DNA microarray assay shows that many cadmium-induced genes are under the control of Zip1, suggesting Zip1 plays a role in cadmium response. Consistently, zip1 mutants are hypersensitive to cadmium and unlike wild type, lose cell viability under this stress. Intriguingly, cadmium exposure results in upregulation of Zip1 levels and leads wild-type cells to growth arrest with reduced cell size, reminiscent of pof1 phenotypes. Our results indicate that Zip1 mediates growth arrest in cadmium response, which is essential to maintain viability. Normally growing cells prevent this response through constitutive ubiquitylation and degradation of Zip1 via SCF(Pof1).
Affiliation:
Laboratory of Cell Regulation, Lincoln's Inn Fields Laboratories, Cancer Research UK, London Research Institute, London, UK.
Citation:
SCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast. 2005, 24 (3):599-610 EMBO J.
Journal:
The EMBO Journal
Issue Date:
9-Feb-2005
URI:
http://hdl.handle.net/10541/74822
DOI:
10.1038/sj.emboj.7600536
PubMed ID:
15660136
Type:
Article
Language:
en
ISSN:
0261-4189
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHarrison, Clare-
dc.contributor.authorKatayama, Satoshi-
dc.contributor.authorDhut, Susheela-
dc.contributor.authorChen, Dongrong-
dc.contributor.authorJones, Nic-
dc.contributor.authorBähler, Jürg-
dc.contributor.authorToda, Takashi-
dc.date.accessioned2009-07-21T16:53:33Z-
dc.date.available2009-07-21T16:53:33Z-
dc.date.issued2005-02-09-
dc.identifier.citationSCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast. 2005, 24 (3):599-610 EMBO J.en
dc.identifier.issn0261-4189-
dc.identifier.pmid15660136-
dc.identifier.doi10.1038/sj.emboj.7600536-
dc.identifier.urihttp://hdl.handle.net/10541/74822-
dc.description.abstractUbiquitin-dependent proteolysis regulates gene expression in many eukaryotic systems. Pof1 is an essential fission yeast F-box protein that is homologous to budding yeast Met30. Temperature-sensitive pof1 mutants display acute growth arrest with small cell size. Extragenic suppressor analysis identified Zip1, a bZIP (basic leucine zipper) transcription factor, as a target for Pof1. We show Zip1 is stabilized in pof1 mutants, Pof1 binds only phosphorylated forms of Zip1, and Zip1 is ubiquitylated in vivo, indicating that Zip1 is a substrate of SCF(Pof1). Genome-wide DNA microarray assay shows that many cadmium-induced genes are under the control of Zip1, suggesting Zip1 plays a role in cadmium response. Consistently, zip1 mutants are hypersensitive to cadmium and unlike wild type, lose cell viability under this stress. Intriguingly, cadmium exposure results in upregulation of Zip1 levels and leads wild-type cells to growth arrest with reduced cell size, reminiscent of pof1 phenotypes. Our results indicate that Zip1 mediates growth arrest in cadmium response, which is essential to maintain viability. Normally growing cells prevent this response through constitutive ubiquitylation and degradation of Zip1 via SCF(Pof1).en
dc.language.isoenen
dc.subject.meshBasic-Leucine Zipper Transcription Factors-
dc.subject.meshCadmium-
dc.subject.meshCarrier Proteins-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshF-Box Proteins-
dc.subject.meshG-Box Binding Factors-
dc.subject.meshGenes, Fungal-
dc.subject.meshModels, Biological-
dc.subject.meshMutation-
dc.subject.meshPhosphorylation-
dc.subject.meshProtein Binding-
dc.subject.meshSKP Cullin F-Box Protein Ligases-
dc.subject.meshSchizosaccharomyces-
dc.subject.meshSchizosaccharomyces pombe Proteins-
dc.subject.meshSuppression, Genetic-
dc.subject.meshTemperature-
dc.subject.meshTranscription Factors-
dc.subject.meshUbiquitin-
dc.subject.meshUp-Regulation-
dc.titleSCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast.en
dc.typeArticleen
dc.contributor.departmentLaboratory of Cell Regulation, Lincoln's Inn Fields Laboratories, Cancer Research UK, London Research Institute, London, UK.en
dc.identifier.journalThe EMBO Journalen

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