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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hürlimann, Hans Caspar Pinson, Benoît Daignan-fornier, Bertrand Moenner, Michel Saint-marc, Christelle Albrecht, Delphine Ceschin, Johanna Violo, Typhaine |
| Description | Author Affiliation: Ceschin J ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.); Hürlimann HC ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.); Saint-Marc C ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.); Albrecht D ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.); Violo T ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.); Moenner M ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.); Daignan-Fornier B ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France b.daignan-fornier@ibgc.cnrs.fr.); Pinson B ( From the Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.) |
| Abstract | 5-Aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 39 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-09-25 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adenine Phosphoribosyltransferase Antagonists & Inhibitors Aminoimidazole Carboxamide Analogs & Derivatives Cell Proliferation Drug Effects Nucleotides Metabolism Ribonucleotides Pharmacology Saccharomyces Cerevisiae Proteins Saccharomyces Cerevisiae Genetics Cell Line Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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