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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pinson, Benoît Daignan-fornier, Bertrand Moenner, Michel Laporte, Jean Saint-marc, Christelle Philippe, Chloé Ceschin, Johanna Labriet, Adrien |
| Description | Author Affiliation: Ceschin J ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France.); Saint-Marc C ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France.); Laporte J ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France.); Labriet A ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France.); Philippe C ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France.); Moenner M ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France.); Daignan-Fornier B ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France.); Pinson B ( From the Université de Bordeaux IBGC UMR 5095 1, F-33077 Bordeaux, France and the Centre National de la Recherche Scientifique IBGC UMR 5095 1, F-33077 Bordeaux, France benoit.pinson@ibgc.cnrs.fr.) |
| Abstract | 5-Aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAr) is the precursor of the active monophosphate form (AICAR), a small molecule with potent anti-proliferative and low energy mimetic properties. The molecular bases for AICAR toxicity at the cellular level are poorly understood. Here, we report the isolation and characterization of several yeast AICAr-hypersensitive mutants. Identification of the cognate genes allowed us to establish that thiamine transporters Thi7 and Thi72 can efficiently take up AICAr under conditions where they are overexpressed. We establish that, under standard growth conditions, Nrt1, the nicotinamide riboside carrier, is the major AICAr transporter in yeast. A study of AICAR accumulation in human cells revealed substantial disparities among cell lines and confirmed that AICAr enters cells via purine nucleoside transporters. Together, our results point to significant differences between yeast and human cells for both AICAr uptake and AICAR accumulation. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 24 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-06-13 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Aminoimidazole Carboxamide Analogs & Derivatives Membrane Transport Proteins Metabolism Ribonucleotides Pharmacology Saccharomyces Cerevisiae Proteins Saccharomyces Cerevisiae Animals Cell Line Cell Line, Tumor Genetics Mice Mutation Nucleoside Transport Proteins Drug Effects Thiamine 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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