Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells
Chen S, Tjin C, Gao X, Xue Y, Jiao H, Zhang R, Wu M, He Z, Ellman J, Ha Y. Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2002486118. PMID: 34001596, PMCID: PMC8166193, DOI: 10.1073/pnas.2002486118.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein Kinase KinasesAnimalsEnergy MetabolismHumansInsulinInsulin Receptor Substrate ProteinsMechanistic Target of Rapamycin Complex 1MiceMuscle Fibers, SkeletalNeoplasmsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Ribosomal Protein S6 Kinases, 70-kDaSignal TransductionSmall Molecule LibrariesTumor Suppressor Protein p53ConceptsP53-null tumor cellsMost human cancer cellsCell energy homeostasisCell energy metabolismTumor suppressor genePI5P4KHuman cancer cellsGenetic experimentsDifferentiated myotubesAMPK activationStructural basisKinase activityEnergy stressMetabolic regulationSuppressor geneFunction mutationsLate-onset tumorsSubstrate loopP53 tumor suppressor geneChemical probesPI3KCell typesExquisite specificityEnergy metabolismTumor cells