MDM2 promotes CELF6 ubiquitination-dependent degradation to promote neuroblastoma cell proliferation.

ABSTRACT: The ubiquitin-proteasome system plays a crucial role in neuroblastoma progression, yet the regulation of key degradation targets remains incompletely understood. By integrating transcriptomic and proteomic data, we identified nine candidate proteins, including CELF6, whose degradation is potentially mediated by ubiquitination. Survival analyses revealed that high CELF6 expression correlated with a favorable prognosis. Functional assays demonstrated that CELF6 suppresses neuroblastoma cell proliferation without affecting apoptosis. Mechanistically, the E3 ubiquitin ligase MDM2 directly interacts with CELF6, promoting its degradation via K48-linked ubiquitination. MDM2 overexpression accelerates CELF6 degradation, while its inhibition stabilizes CELF6 protein levels, an effect reversed by pr

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC12540984 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature