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Mechanisms of AICAR in lung cancer

ABSTRACT: Mechanisms of AICAR in lung cancer

PROVIDER: PRJNA816863 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18339687_1.fastq.gz	Fastqsanger.gz
	SRR18339687_2.fastq.gz	Fastqsanger.gz
	SRR18339688_1.fastq.gz	Fastqsanger.gz
	SRR18339688_2.fastq.gz	Fastqsanger.gz
	SRR18339689_1.fastq.gz	Fastqsanger.gz

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Mechanisms of AICAR in lung cancer

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Effect of AICAR monophosphate and AICAr riboside accumulation on global transcription

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.

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Project description:To identify genes transcriptionally regulated by AICAR under cellular stress, We treated NALM6 cells for 45 min with vehicle (DMSO) or AICAR (15 mM), and examined their RNA profile using RNA-Seq. The immediate early genes (IEGs) were identified as a subset of genes downregulated by AICAR.

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