title: SCF(Pof1)-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast.
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).
authors.affiliation: Laboratory of Cell Regulation, Lincoln's Inn Fields Laboratories, Cancer Research UK, London Research Institute, London, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Harrison
authors.forename: Satoshi
authors.initials: S
authors.lastname: Katayama
authors.forename: Susheela
authors.initials: S
authors.lastname: Dhut
authors.forename: Dongrong
authors.initials: D
authors.lastname: Chen
authors.forename: Nic
authors.initials: N
authors.lastname: Jones
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors; D002104:Cadmium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D051790:G-Box Binding Factors; D005800:Genes, Fungal / Q000187:drug effects; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013489:Suppression, Genetic; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D051790:G-Box Binding Factors; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D002104:Cadmium; D044843:SKP Cullin F-Box Protein Ligases