Project description:AICAR monophosphate (5-Aminoimidazole-4-carboxamide ribonucleotide) is a metabolic intermediate of the de novo purine synthesis pathway presenting highly promising metabolic and antiproliferative properties. Yeast mutants accumulating AICAR are auxotroph for histidine. A screening for suppressors of this phenotype identified recessive and dominant mutants that result in lowering intracellular AICAR concentration. The recessive mutants affect adenosine kinase which is shown here to catalyze the phosphorylation of AICAR riboside in yeast. The dominant mutants strongly enhance the capacity of the alkaline phosphatase Pho13p to dephosphorylate succinyl-AICAR monophosphate into the non-toxic riboside form. By combining these mutants to transcriptomic and metabolomic analyses, we establish that in yeast both toxic and physiological responses to AICAR are linked to the concentration of the monophosphate form, while the nucleoside moiety has no effect even at high concentration. Finally, we establish that (S)AICAR concentration varies under physiological conditions, thus modulating transcriptional regulation of purine pathway genes. This SuperSeries is composed of the SubSeries listed below.
2011-07-11 | GSE29324 | GEO
Project description:Effect of AICAR and SAICAR accumulation on global transcription
Project description:We investigated the effects of AICAR and SAICAR accumulation on transcriptional regulation of purine biosynthesis and other metabolic pathways. These data were compared to those obtained in the ade16ade17 vs WT data set to determine the transcriptional effects associated to AICAR/SAICAR accumulation and those due to ade16 and ade17 deletions. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating or lacking AICAR and SAICAR nucleotide derivatives.
Project description:We investigated the role of Bas1p in the transcriptional response due to AICAR and SAICAR accumulation. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC. Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating AICAR and SAICAR in a bas1 deletion context.
Project description:We investigated the role of Pho4p in the transcriptional response associated to AICAR and SAICAR accumulation. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC. Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating AICAR and SAICAR in a pho4 deletion context.
Project description:We investigated the role of Pho2p in the transcriptional response associated to AICAR and SAICAR accumulation. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC. Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating AICAR and SAICAR in a pho2 deletion context.
Project description:We investigated the effects of AICAR and SAICAR accumulation on transcriptional regulation of purine biosynthesis and other metabolic pathways. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC. Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating or not AICAR and SAICAR nucleotide derivatives.