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Projects. Life and Earth Sciences

Identification of the nucleotide cellular sensor and its interactome

Lead Researcher: Marçal Pastor Anglada
Research Centre: CIBEREHD-Universidad de Barcelona.

Abstract: 

Marçal Pastor AngladaMechanisms controlling the switch from nucleoside and nucleobase salvage to activation of de novo purine and pyrimidine nucleotide biosynthesis in cells are not known. However nucleotide pools are crucial for normal cell survival and proliferation. Indeed, purine and pyrimidine imbalance as well as poor nucleotide bioavailability appear to be crucial for oncogenesis. This project is based upon the hypothesis that cells must contain a sensing mechanism responsible for this switch, promoting nucleotide biosynthesis when extracellular nucleoside and nucleobase availability is low. Our laboratory has recently obtained the first biochemical evidence supporting the view that protein-protein interactions may favor this type of regulation. In particular two key enzymes implicated in salvage and de novo nucleotide biosynthesis are likely to physically interact. A first bioinformatics approach strongly supports this biochemical evidence. We hypothesize that the interactome of this nucleotide sensor is crucial for proliferation in differentiated cells, whereas this network might be altered during oncogenesis and cancer. By understanding protein-protein interactions in nucleotide metabolism we hope to identify novel targets for pharmacological intervention.


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