The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells.

ABSTRACT: Cullin-RING ligases (CRLs) and the anaphase-promoting complex/cyclosome (APC/C) are two major multi-subunit ubiquitin ligases essential for protein homeostasis. The underlying mechanism and biological consequence of their crosstalk remain elusive. Here, tandem affinity purification followed by LC-MS/MS is employed, and identified APC11-the RING subunit of APC/C-as a bona fide binding partner of CUL5, the scaffold of CRL5. On one hand, APC11 interacts with CUL5 and inhibits its neddylation. Consequently, APC11 knockdown enhances CUL5 neddylation by promoting its interaction with the neddylation E2 UBE2F. This leads to the degradation of SOCS3, a substrate receptor of CRL5, and the subsequent accumulation of its substrate, integrin β1, ultimately promoting cancer metastasis. On the other han

SUBMITTER: Cui D 

PROVIDER: S-EPMC12806337 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature