![]() The authors discovered that tomato bushy stunt virus (TBSV) co-opts the glycolytic ATP-generating Pgk1 phosphoglycerate kinase to facilitate the. Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1QH, UK. Author summary Positive-strand (+)RNA viruses build replication organelles with the help of many co-opted cellular factors and by usurping cellular metabolites and energy, which frequently lead to disease states in plants, animals and humans. These results demonstrate therapeutic potential of the compound series. Compound treatment modulates these interactions and also affects Shelterin complex composition, while conferring cellular protection from cytotoxicity due to bleomycin and desferroxamine. Intriguingly, PGK1 and DJ1 bind to TRF2 and telomeric DNA. Glucose homeostasis and oxidative stress are linked to telomere signaling and exemplar compound CRT0063465 blocked hypoglycemic telomere shortening. In vitro binding and structural analyses confirmed these targets, suggesting that PGK1/DJ1 interact, which we confirmed by immunoprecipitation. We performed structure-activity studies on the series to develop a photoaffinity probe to deconvolute the cellular targets. We report identification and characterization of a pyrazolopyrimidine compound series identified from screens focused on cell immortality and whose targets are glycolytic kinase PGK1 and oxidative stress sensor DJ1. ![]() New agents targeting these processes might provide therapeutic opportunities, including chemoprevention strategies against cancer predisposition. Telomere signaling and metabolic dysfunction are hallmarks of cell aging. Diversity, Equity, Inclusion, and Access.Citation, Usage, Privacy Policies, Logo.Biologically Interesting Molecule Reference Dictionary (BIRD).
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