Enzymes of nucleoside and nucleotide metabolism regulate important cellular processes with potential impacts on nucleotide-unrelated parameters. We have used a set of CRISPR/Cas9-modified cell models expressing both, one, or none of the 5′-nucleotidases cN-II and CD73, together with RNA sequencing and targeted metabolomics, to decipher new regulatory roles of these proteins. We observed important transcriptional modifications between models as well as upon exposure to adenosine. Metabolite content varied differently between cell models in response to adenosine exposure but was rather similar in control conditions. Our original cell models allowed us to identify a new unobvious link between proteins in the nucleotide metabolism and other cellular pathways. Further analyses of our models, including additional experiments, could help us to better understand some of the roles played by these enzymes.
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The nucleotide metabolism has been targeted for many years and in various clinical settings, including cancer.
The increased knowledge of certain enzymes involved in this metabolism and in associated cellular processes accumulated
over the last few years, gives important information to the druggability of certain proteins and to the use of inhibitors for
others. Here, we review recent data on such enzymes with major interest in drug development, i.e. SAMHD1 and the proteins of the NUDIX family. These include information on their roles in cancer progression, correlations with clinical outcome in cancer patients, and development and study of enzymatic inhibitors.
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