FBXO9 mediated the ubiquitination and degradation of YAP in a GSK-3β-dependent manner.

ABSTRACT: The Hippo signaling pathway effector YAP (Yes-associated protein) serves as a critical transcriptional regulator involved in a wide range of biological processes, including oncogenesis. Despite its potential as a therapeutic target, pharmacologically targeting the Hippo/YAP axis remains challenging, necessitating further exploration of the mechanisms governing YAP regulation. In this study, we identify the Cullin-RING E3 ligase complex SCF-FBXO9-CRL1 as a novel posttranslational regulator of YAP stability. Mechanistically, FBXO9 recognizes YAP through a conserved degron motif and facilitates its K48-linked polyubiquitination at lysine 76 (K76), thereby promoting proteasomal degradation. Notably, we demonstrate that phosphorylation of YAP at Ser338 and Thr342 by GSK-3β primes YAP for FBXO9

SUBMITTER: Jin Y 

PROVIDER: S-EPMC12509758 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature