Recruitment to the Proteasome Is Necessary but Not Sufficient for Chemically Induced, Ubiquitin-Independent Degradation of Native Proteins.

ABSTRACT: Targeted protein degradation (TPD) is a promising strategy for drug development. Most degraders function by forcing the association of the target protein (TP) with an E3 Ubiquitin (Ub) ligase, which, in favorable cases, results in the polyubiquitylation of the TP and its subsequent degradation by the 26S proteasome. An alternative strategy would be to create chemical dimerizers that bypass the requirement for polyubiquitylation by recruiting the target protein directly to the proteasome. Direct-to-proteasome degraders (DPDs) may exhibit different characteristics than ubiquitin-dependent degraders, but few studies of this type of TPD have been published, largely due to the dearth of suitable proteasome ligands. To facilitate studies of DPDs, we report here a mammalian cell line in which the

SUBMITTER: Balzarini M 

PROVIDER: S-EPMC11707830 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature