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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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
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author Li, Junjun
Peng, Jin
Wu, Lingzhi
Shen, Xiang
Zhen, Xinghua
Zhang, Yimao
Ma, Huailu
Xu, Yongfeng
Xiong, Qunli
Zhu, Qing
Zhang, Pumin
author_facet Li, Junjun
Peng, Jin
Wu, Lingzhi
Shen, Xiang
Zhen, Xinghua
Zhang, Yimao
Ma, Huailu
Xu, Yongfeng
Xiong, Qunli
Zhu, Qing
Zhang, Pumin
author_sort Li, Junjun
collection PubMed
description 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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spelling pubmed-104046172023-08-08 The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells Li, Junjun Peng, Jin Wu, Lingzhi Shen, Xiang Zhen, Xinghua Zhang, Yimao Ma, Huailu Xu, Yongfeng Xiong, Qunli Zhu, Qing Zhang, Pumin J Biol Chem Research Article 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. American Society for Biochemistry and Molecular Biology 2023-05-23 /pmc/articles/PMC10404617/ /pubmed/37230388 http://dx.doi.org/10.1016/j.jbc.2023.104856 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Li, Junjun
Peng, Jin
Wu, Lingzhi
Shen, Xiang
Zhen, Xinghua
Zhang, Yimao
Ma, Huailu
Xu, Yongfeng
Xiong, Qunli
Zhu, Qing
Zhang, Pumin
The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells
title The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells
title_full The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells
title_fullStr The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells
title_full_unstemmed The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells
title_short The deubiquitinase USP28 maintains the expression of the transcription factor MYCN and is essential in neuroblastoma cells
title_sort deubiquitinase usp28 maintains the expression of the transcription factor mycn and is essential in neuroblastoma cells
topic Research Article
url 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
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