Hijacking Methyl Reader Proteins for Nuclear-Specific Protein Degradation
Dhanusha A. Nalawansha, Ke Li, John Hines, Craig M. Crews
Abstract
E3 ligase complex and targets methylated proteins for proteasomal degradation. By co-opting this natural mechanism, we report the design and biological evaluation of L3MBTL3-recruiting PROTACs and demonstrate nuclear-specific degradation of FKBP12 and BRD2. We envision this as a generalizable approach to utilize other reader protein-associated E3 ligase complexes in PROTAC design to expand the E3 ligase toolbox and explore the full potential of TPD.
Topics & Concepts
Ubiquitin ligaseChemistryProtein degradationDNA ligaseUbiquitinDegradation (telecommunications)CereblonProteasomeComputational biologyFKBPTarget proteinToolboxCell biologyDrug discoveryBiochemistryEnzymeBiologyGeneComputer scienceProgramming languageTelecommunicationsProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysHistone Deacetylase Inhibitors Research