Document Detail


Metabolic intermediates selectively stimulate transcription factor interaction and modulate phosphate and purine pathways.
MedLine Citation:
PMID:  19528318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cells use strategic metabolites to sense the metabolome and accordingly modulate gene expression. Here, we show that the purine and phosphate pathways are positively regulated by the metabolic intermediate AICAR (5'-phosphoribosyl-5-amino-4-imidazole carboxamide). The transcription factor Pho2p is required for up-regulation of all AICAR-responsive genes. Accordingly, the binding of Pho2p to purine and phosphate pathway gene promoters is enhanced upon AICAR accumulation. In vitro, AICAR binds both Pho2p and Pho4p transcription factors and stimulates the interaction between Pho2p and either Bas1p or Pho4p in vivo. In contrast, SAICAR (succinyl-AICAR) only affects Pho2p-Bas1p interaction and specifically up-regulates purine regulon genes. Together, our data show that Bas1p and Pho4p compete for Pho2p binding, hence leading to the concerted regulation of cellular nucleotide synthesis and phosphate consumption.
Authors:
Benoît Pinson; Sabine Vaur; Isabelle Sagot; Fanny Coulpier; Sophie Lemoine; Bertrand Daignan-Fornier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  23     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-16     Completed Date:  2009-06-17     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1399-407     Citation Subset:  IM    
Affiliation:
Université de Bordeaux, Institut de Biochimie et Génétique Cellulaires, Bordeaux 33076, France.
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MeSH Terms
Descriptor/Qualifier:
Aminoimidazole Carboxamide / analogs & derivatives,  metabolism
Cell Nucleus / metabolism
DNA-Binding Proteins / metabolism
Gene Expression Regulation*
Homeodomain Proteins / metabolism
Homeostasis
Phosphates / metabolism*
Promoter Regions, Genetic / genetics
Protein Binding
Protein Transport
Purines / biosynthesis*
Regulon / genetics
Ribonucleotides / metabolism
Saccharomyces cerevisiae / genetics,  physiology*
Saccharomyces cerevisiae Proteins / metabolism
Trans-Activators / metabolism
Transcription Factors / metabolism*
Up-Regulation
Chemical
Reg. No./Substance:
0/BAS1 protein, S cerevisiae; 0/DNA-Binding Proteins; 0/Homeodomain Proteins; 0/PHO2 protein, S cerevisiae; 0/PHO4 protein, S cerevisiae; 0/Phosphates; 0/Purines; 0/Ribonucleotides; 0/Saccharomyces cerevisiae Proteins; 0/Trans-Activators; 0/Transcription Factors; 120-73-0/purine; 3031-94-5/AICA ribonucleotide; 360-97-4/Aminoimidazole Carboxamide
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