CBL ubiquitin ligase targets translation as a degrader E3.

ABSTRACT: Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional molecules that recruit an ubiquitin ligase (E3) and a neo-substrate into a ternary complex, enabling selective protein degradation. Despite the presence of over 600 E3s, only a handful are utilised in PROTAC application, potentially limiting the number of druggable targets. Here, we investigate whether Casitas B-cell lymphoma (CBL) can be harnessed as a degrader E3 to promote ubiquitination and degradation of the eukaryotic translation initiation factor 4E (eIF4E). Using a selective CBL binding peptide, CBLock, we demonstrate that CBL facilitates the ubiquitination of CBLock-eIF4E fusion in cells and in in vitro reconstituted assays. We further developed peptidic PROTACs, termed eIFTerminators, by linking CBLock to an e

SUBMITTER: Wicks AT 

PROVIDER: S-EPMC12774438 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature