Identification of Yeast and Human 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAr) Transporters

作者：Ceschin Johanna; Saint Marc Christelle; Laporte Jean; Labriet Adrien; Philippe Chloe; Moenner Michel; Daignan Fornier Bertrand; Pinson Benoit^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289(24): 16844-16854.

DOI：10.1074/jbc.M114.551192

5-Aminoimidazole-4-carboxamide-1-beta-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.

• 出版日期2014-6-13