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

Year: 2025

Type: article

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 proteasome inhibitors. Furthermore, MDM2-driven neuroblastoma cell proliferation is dependent on CELF6 depletion. These findings establish MDM2 as a key regulator of CELF6 stability and highlight the MDM2-CELF6 axis as a potential therapeutic target in neuroblastoma.

Source: Cell Death and Disease

DOI: 10.1038/s41419-025-08048-3

Authors: Zhenzhen Zhao, Bao Zhang, Xu Zhang, Changchun Li

Institution: Children's Hospital of Chongqing Medical University

Language: English

Topic: Neuroblastoma Research and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,990