MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4B^DCAF13 E3 Ligase in Osteosarcoma Cells.

ABSTRACT: Cullins, critical members of the cullin-RING ubiquitin ligases (CRLs), are often aberrantly expressed in different cancers. However, the underlying mechanisms regarding aberrant expression of these cullins and the specific substrates of CRLs in different cancers are mostly unknown. Here, we demonstrate that overexpressed CUL4B in human osteosarcoma cells forms an E3 complex with DNA damage binding protein 1 (DDB1) and DDB1- and CUL4-associated factor 13 (DCAF13). In vitro and in vivo analyses indicated that the CRL4B^DCAF13 E3 ligase specifically recognized the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) for degradation, and disruption of this E3 ligase resulted in PTEN accumulation. Further analyses indicated that miR-300 directly targeted the

SUBMITTER: Chen Z 

PROVIDER: S-EPMC5768150 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature