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Targeting Endogenous K-RAS for Degradation through the Affinity-Directed Protein Missile System

Sascha Röth, Thomas Macartney, Agnieszka Konopacka, Kwok-Ho Chan, Houjiang Zhou, Markus A. Queisser, Gopal P. Sapkota

2020Cell chemical biology67 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

EndogenyMissileDegradation (telecommunications)ChemistryProtein degradationCell biologyComputer scienceBiochemistryBiologyEngineeringAerospace engineeringTelecommunicationsProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysSignaling Pathways in Disease