Small molecule TSC01682 inhibits osteosarcoma cell growth by specifically disrupting the CUL4B-DDB1 interaction and decreasing the ubiquitination of CRL4B E3 ligase substrates.

ABSTRACT: The direct interaction between Cullin 4B (CUL4B) and DNA damage-binding protein 1 (DDB1) is required for the assembly of Cullin4B-RING E3 ligase complex (CRL4B), which are involved in the tumorigenesis of osteosarcoma through ubiquitinating and degrading multiple tumor suppressors and cell cycle regulators. Thus, targeting CUL4B-DDB1 interaction to prevent the assembly of CRL4B may be a potent approach to inhibit osteosarcoma cell growth. In the present study, we identified six naturally-sourced small molecules that can specifically disrupt the CUL4B-DDB1 interaction using an in vitro high-throughput screening (HTS) system in yeast. We focused our investigation on revealing the molecular effects of TSC01682, the most active compound capable of inhibiting osteosarcoma c

SUBMITTER: Chen B 

PROVIDER: S-EPMC6780663 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature