grant
Regulation of Nuclear Akt by p53, MDM2 and Phosphoinositide Lipids Roles in Oncogenic Transformation and Tumor Progression
Organization UNIVERSITY OF WISCONSIN-MADISONLocation MADISON, UNITED STATESPosted 1 Aug 2024Deadline 31 Jul 2029
NIHUS FederalResearch GrantFY20251-Phosphatidylinositol 4-KinaseAKT Signaling PathwayATP-protein phosphotransferaseAntioncogene Protein p53ApoptosisApoptosis PathwayBindingBiologicalBreast CancerBreast Cancer ModelBreast tumor modelCancer BiologyCancersCell Communication and SignalingCell Death InhibitionCell Membrane LipidsCell NucleusCell SignalingCell SurvivalCell ViabilityCell modelCellular ExpansionCellular GrowthCellular Tumor Antigen P53Cellular modelChiro-InositolClinicClinicalComplexDoseDrug TargetingEC 2.7.1.67ESI geneESI proteinElastase-Specific InhibitorEnzyme GeneEnzymesFamily memberGene TranscriptionGenerationsGenetic TranscriptionGenomicsGenotoxic StressHDM2Heat shock proteinsInositide PhospholipidsInositolInositol PhosphoglyceridesInositol PhospholipidsIntracellular Communication and SignalingKST geneKST proteinKinase Family GeneKinasesLabelLigaseLigase GeneLinkLipidsMDM2MDM2 geneMDMX proteinMMAC1MMAC1 proteinMalignant Breast NeoplasmMalignant NeoplasmsMalignant TumorMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMdm-2 proteinMembraneMembrane LipidsMesoinositolMetabolicModelingModificationMolecularMolecular InteractionMolecular Tumor SuppressionMutateMutated in Multiple Advanced Cancers 1NPIKNuclearNucleusOncogenicOncoprotein MDM2Oncoprotein p53OutcomeP53PDK1PDPK1PDPK1 genePH DomainPHTS genePHTS proteinPI 4-KinasePI3PI3 genePI4PI4K92PI4KBetaPRO0461PTENPTEN genePTEN proteinPTEN1Pathway interactionsPhosphatase and Tensin HomologPhosphatase and Tensin Homolog Deleted on Chromosome 10PhosphatasesPhosphate-Binding ProteinsPhosphatidyl InositolPhosphatidyl Inositol PhosphatesPhosphatidylinositiol KinasePhosphatidylinositol 4-KinasePhosphatidylinositol 4-Kinase BetaPhosphatidylinositol 4-Kinase, Catalytic, BetaPhosphatidylinositol 4-Kinase, Type III, BetaPhosphatidylinositol Kinase Type IIPhosphatidylinositol PhosphatesPhosphatidylinositolsPhosphohydrolasesPhosphoinositide KinasePhosphoinositide-4-Kinase Catalytic Beta PolypeptidePhosphoinositidesPhosphomonoesterasesPhosphoprotein P53Phosphoprotein pp53Phosphoric Monoester HydrolasesPhosphorylationPhosphotransferase GenePhosphotransferasesPleckstrin-Homology DomainPolyphosphoinositidesProgrammed Cell DeathProliferatingProtease Inhibitor 4Protein KinaseProtein PhosphorylationProtein TP53Proteinase Inhibitor 3ProteinsPtdInsPtdIns 4-KinasePublicationsRNA ExpressionReactionRegulationResearch SpecimenRoleSERPINA4SERPINA4 geneSKALPScientific PublicationSignal TransductionSignal Transduction SystemsSignalingSiteSpecimenStressSynthetasesTP53TP53 geneTRAPPIN 2TRP53TestingTherapeuticTissue Kallikrein InhibitorTranscriptionTransphosphorylasesTumor PromotionTumor Protein p53Tumor Protein p53 GeneTumor SuppressionTumor Suppressor ProteinsUbiquitin Ligase Component GeneUbiquitin Ligase GeneWortmannin-Sensitive Phosphatidylinositol 4-Kinasebiologicbiological signal transductioncancer progressioncell growthelafinglycogen synthase a kinasehydroxyalkyl protein kinaseinositol polyphosphate multikinaseinsightkallistatinkinase inhibitormIPMKmalignancymalignant breast tumormammary cancer modelmammary tumor modelmdm-2 oncogene proteinmdm2 proteinmembrane structuremouse modelmurine modelmutantmutated in multiple advanced cancers 1 proteinneoplasm progressionneoplasm/cancerneoplastic progressionnovelp53 Antigenp53 Genesp53 Tumor Suppressorp53-Binding Protein MDM2pathwayphosphatase and tensin homologue on chromosome tenphosphorylase b kinase kinaseprotein p53recruitresponsescaffoldscaffoldingskin-derived antileukoproteinasesocial rolestress proteintherapeutic targettumor growthtumor initiationtumor progressiontumor suppressorubiquitin ligase
Description preview
PROJECT SUMMARY: 30 lines.
The canonical phosphoinositide (PI) 3-kinase (PI3K)/Akt signaling pathway uses free membrane PI lipid to
regulate cell growth and is frequently hyperactivated in cancer. Akt is also activated in the nucleus by poorly
understood mechanisms. We discovered a nuclear PI3K/Akt pathway composed of PI kinases/phosphatases
that…
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