Inhibition of SCF^KDM2A/USP22-dependent nuclear β-catenin ubiquitylation mediates cerebral ischemic tolerance.

ABSTRACT: Hypoxic postconditioning (HPC) was reported to stabilize nuclear β-catenin by inhibiting lysine (K)-specific demethylase 2 A (KDM2A) in hippocampal CA1 against transient global cerebral ischemia (tGCI). Herein we investigate how HPC inhibits the K48-linked poly-ubiquitination (K48-Ub)-related degradation of nuclear β-catenin in CA1 after tGCI. We confirmed that SCF^KDM2A complex targets nuclear β-catenin for degradation via ubiquitin proteasome pathway in vitro. HPC reduced SCF^KDM2A complex and the K48-Ub of β-catenin, and increased ubiquitin-specific peptidase 22 (USP22) in nucleus after tGCI. Furthermore, KDM2A knockdown decreased the K48-Ub of nuclear β-catenin and nuclear β-catenin-SCF^KDM2A complex interaction after tGCI. Moreover, β-catenin knockdown su

SUBMITTER: Zuo Y 

PROVIDER: S-EPMC11814243 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature