Cell chemical biology · 2020 · 67 citations · 58 references
MedicineMolecular BiologyOncologyDrug DiscoveryMolecular OncologyOncogenesCrispr-cas SystemsEnzymatic Cleavage StrategiesProteolytic ProcessingRas Family OncogenesTargeted Cancer TherapyTherapeutic Protein EngineeringCrispr-cas9 KnockoutOncogenic Ras MutationsProteasomal TurnoverProtein Proteolysis EngineeringProteolysis AnalysisProteolytic Stability ControlRas-targeted TherapiesTargeted Protein Degradation
led to robust proteasomal degradation of endogenous GFP-K-RAS, while expression of anti-HRAS-targeting AdPROM in different cell lines resulted in the degradation of both GFP-tagged and untagged K-RAS, and untagged H-RAS. Our findings imply that endogenous RAS proteins can be targeted for proteolysis, supporting the idea of an alternative therapeutic approach to these undruggable targets.
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
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