Document Detail


Copper induces cytoplasmic retention of fission yeast transcription factor cuf1.
MedLine Citation:
PMID:  16467469     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Copper homeostasis within the cell is established and preserved by different mechanisms. Changes in gene expression constitute a way of maintaining this homeostasis. In Schizosaccharomyces pombe, the Cuf1 transcription factor is critical for the activation of copper transport gene expression under conditions of copper starvation. However, in the presence of elevated intracellular levels of copper, the mechanism of Cuf1 inactivation to turn off gene expression remains unclear. In this study, we provide evidence that inactivation of copper transport gene expression by Cuf1 is achieved through a copper-dependent, cytosolic retention of Cuf1. We identify a minimal nuclear localization sequence (NLS) between amino acids 11 to 53 within the Cuf1 N terminus. Deletion of this region and specific mutation of the Lys13, Arg16, Arg19, Lys24, Arg28, Lys45, Arg47, Arg50, and Arg53 residues to alanine within this putative NLS is sufficient to abrogate nuclear targeting of Cuf1. Under conditions of copper starvation, Cuf1 resides in the nucleus. However, in the presence of excess copper as well as silver ions, Cuf1 is sequestered in the cytoplasm, a process which requires the putative copper binding motif, 328Cys-X-Cys-X3-Cys-X-Cys-X2-Cys-X2-His342 (designated C-rich), within the C-terminal region of Cuf1. Deletion of this region and mutation of the Cys residues within the C-rich motif result in constitutive nuclear localization of Cuf1. By coexpressing the Cuf1 N terminus with its C terminus in trans and by using a two-hybrid assay, we show that these domains physically interact with each other in a copper-dependent manner. We propose a model wherein copper induces conformational changes in Cuf1 that promote a physical interaction between the Cuf1 N terminus and the C-rich motif in the C terminus that masks the NLS. Cuf1 is thereby sequestered in the cytosol under conditions of copper excess, thereby extinguishing copper transport gene expression.
Authors:
Jude Beaudoin; Simon Labbé
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Eukaryotic cell     Volume:  5     ISSN:  1535-9778     ISO Abbreviation:  Eukaryotic Cell     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-09     Completed Date:  2006-05-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  101130731     Medline TA:  Eukaryot Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  277-92     Citation Subset:  IM    
Affiliation:
Département de Biochimie, Faculté de médecine, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, Québec J1H 5N4, Canada.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus / drug effects
Amino Acid Motifs
Amino Acid Sequence
Amino Acids, Basic
Cell Nucleus / metabolism
Copper / pharmacology*
Cytoplasm / drug effects*,  metabolism*
Metals / pharmacology
Models, Biological
Molecular Sequence Data
Nuclear Localization Signals
Protein Binding
Protein Transport / drug effects
Recombinant Fusion Proteins
Schizosaccharomyces / cytology,  drug effects,  genetics*
Schizosaccharomyces pombe Proteins / chemistry,  metabolism*
Silver / pharmacology
Transcription Factors / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Amino Acids, Basic; 0/Cuf1 protein, S pombe; 0/Metals; 0/Nuclear Localization Signals; 0/Recombinant Fusion Proteins; 0/Schizosaccharomyces pombe Proteins; 0/Transcription Factors; 7440-22-4/Silver; 7440-50-8/Copper
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