SCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast.
Authors
Harrison, ClareKatayama, Satoshi
Dhut, Susheela
Chen, Dongrong
Jones, Nic
Bähler, Jürg
Toda, Takashi
Affiliation
Laboratory of Cell Regulation, Lincoln's Inn Fields Laboratories, Cancer Research UK, London Research Institute, London, UK.Issue Date
2005-02-09
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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).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 JournalDOI
10.1038/sj.emboj.7600536PubMed ID
15660136Type
ArticleLanguage
enISSN
0261-4189ae974a485f413a2113503eed53cd6c53
10.1038/sj.emboj.7600536
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