P300 Interacted With N-Myc and Regulated Its Protein Stability via Altering Its Post-Translational Modifications in Neuroblastoma.

Humans N-Myc Proto-Oncogene Protein / genetics Lysine / metabolism Tandem Mass Spectrometry Protein Processing, Post-Translational Neuroblastoma / drug therapy Protein Stability Cell Line, Tumor Gene Expression Regulation, Neoplastic
MYCN interacting proteins neuroblastoma post-translational modifications protein stability

Journal

Molecular & cellular proteomics : MCP
ISSN: 1535-9484
Titre abrégé: Mol Cell Proteomics
Pays: United States
ID NLM: 101125647

Informations de publication

Date de publication:
03 2023
Historique:
received: 25 04 2022
revised: 10 01 2023
accepted: 23 01 2023
medline: 28 3 2023
pubmed: 29 1 2023
entrez: 28 1 2023
Statut: ppublish

Résumé

MYCN amplification is an independent risk factor for poor prognosis in neuroblastoma (NB), but its protein product cannot be directly targeted because of protein structure. Thus, this study aimed to explore novel ways to indirectly target N-Myc by regulating its post-translational modifications (PTMs) and therefore protein stability. N-Myc coimmunoprecipitation combined with HPLC-MS/MS identified 16 PTM residues and 114 potential N-Myc-interacting proteins. Notably, both acetylation and ubiquitination were identified on lysine 199 of N-Myc. We then discovered that p300, which can interact with N-Myc, modulated the protein stability of N-Myc in MYCN-amplified NB cell lines and simultaneously regulated the acetylation level and ubiquitination level on lysine-199 of N-Myc protein in vitro. Furthermore, p300 correlated with poor prognosis in NB patients. Taken together, p300 can be considered as a potential therapeutic target to treat MYCN-amplified NB patients, and other identified PTMs and interacting proteins also provide potential targets for further study.

Identifiants

DOI: 10.1016/j.mcpro.2023.100504 PMID: 36708875 PMC: PMC9984901
pubmed: 36708875
pii: S1535-9476(23)00013-0
doi: 10.1016/j.mcpro.2023.100504
pmc: PMC9984901
pii:
doi:

Substances chimiques

N-Myc Proto-Oncogene Protein 0
Lysine K3Z4F929H6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

100504

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare no competing interests.

Auteurs

Cheng Cheng (C)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.

Tian He (T)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.

Kai Chen (K)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.

Yuanxia Cai (Y)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.

Yaoyao Gu (Y)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.

Lijia Pan (L)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.

Peiwen Duan (P)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China.

Yeming Wu (Y)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China; Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China. Electronic address: wuyeming@xinhuamed.com.cn.

Zhixiang Wu (Z)

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, China; Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou, China. Electronic address: wuzhixiang@xinhuamed.com.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines › Protéine du proto-oncogène N-Myc › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés essentiels › Lysine › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Spectrométrie de masse en tandem › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Tumeurs neuroectodermiques primitives › Tumeurs neuroectodermiques primitives périphériques › Neuroblastome › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Stabilité protéique › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › P300 Interacted With N-Myc and Regulated Its...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › P300 Interacted With N-Myc and Regulated Its...