The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells

Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. MYCN gene amplification is highly associated with poor prognosis in high-risk NB patients. In non-MYCN-amplified high-risk NB patients, the expression of c-MYC (MYCC) and its target genes is highly elevated. USP28 as...

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Detalles Bibliográficos
Autores principales: Li, Junjun, Peng, Jin, Wu, Lingzhi, Shen, Xiang, Zhen, Xinghua, Zhang, Yimao, Ma, Huailu, Xu, Yongfeng, Xiong, Qunli, Zhu, Qing, Zhang, Pumin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404617/
https://www.ncbi.nlm.nih.gov/pubmed/37230388
http://dx.doi.org/10.1016/j.jbc.2023.104856
Descripción
Sumario:Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. MYCN gene amplification is highly associated with poor prognosis in high-risk NB patients. In non-MYCN-amplified high-risk NB patients, the expression of c-MYC (MYCC) and its target genes is highly elevated. USP28 as a deubiquitinase is known to regulate the stability of MYCC. We show here USP28 also regulates the stability of MYCN. Genetic depletion or pharmacologic inhibition of the deubiquitinase strongly destabilizes MYCN and stops the growth of NB cells that overexpress MYCN. In addition, MYCC could be similarly destabilized in non-MYCN NB cells by compromising USP28 function. Our results strongly suggest USP28 as a therapeutic target for NB with or without MYCN amplification/overexpression.

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