Niclosamide: CRL4^AMBRA1 mediated degradation of cyclin D1 following mitochondrial membrane depolarization.

ABSTRACT: Targeted protein degradation has emerged as a promising approach in drug discovery, utilizing small molecules like molecular glue degraders to harness the ubiquitin-proteasome pathway for selective degradation of disease-driving proteins. Based on results from proteomics screens we investigated the potential of niclosamide, an FDA-approved anthelmintic drug with a 50 year history in treating tapeworm infections, as a molecular glue degrader targeting the proto-oncogene cyclin D1. Proteomics screens in HCT116 colon carcinoma and KELLY neuroblastoma cells, found that niclosamide induces rapid cyclin D1 degradation through a mechanism involving the ubiquitin-proteasome pathway. A genetic CRISPR screen identified the E3 ligase CRL4^AMBRA1 as a key player in this process. Structure-ac

SUBMITTER: Coomar S 

PROVIDER: S-EPMC12054360 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature