GSK3β Regulates a Novel β-Catenin Degradation Pathway via the GID Complex in Wnt Signaling.

ABSTRACT: The canonical Wnt signaling pathway plays a pivotal role in regulating cell proliferation, differentiation, and tissue homeostasis. These functions are largely regulated through the degradation of β-Catenin. Under Wnt-off conditions, β-Catenin is phosphorylated by the destruction complex, including GSK3β, and subsequently ubiquitinated by the E3 ligase βTrCP, leading to proteasomal degradation. In this study, we identified a regulatory mechanism in which suppression of GSK3β promotes β-Catenin degradation via the GID complex, a conserved multi-subunit E3 ubiquitin ligase. GSK3β knockdown increased β-Catenin ubiquitination and decreased its protein levels in both the cytoplasm and nucleus, independent of βTrCP. This degradation was rescued by knockdown of GID components MAEA and RMND5A, but

SUBMITTER: Shimizu M 

PROVIDER: S-EPMC12628731 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature