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

Cheng Cheng1, Tian He1, Kai Chen1

  • 1Department 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.

Molecular & Cellular Proteomics : MCP
|January 28, 2023
PubMed

Insights

Targeting N-Myc in neuroblastoma (NB) is challenging. This study identified p300 as a key regulator of N-Myc stability, offering a potential therapeutic target for MYCN-amplified NB.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MYCN amplification is a significant prognostic factor in neuroblastoma (NB).
  • The N-Myc protein's structure prevents direct therapeutic targeting.
  • Targeting N-Myc's post-translational modifications (PTMs) offers an indirect therapeutic strategy.

Purpose of the Study:

  • To investigate novel strategies for indirectly targeting N-Myc in neuroblastoma.
  • To identify key regulators of N-Myc post-translational modifications (PTMs) and protein stability.
  • To evaluate the therapeutic potential of targeting N-Myc-regulating proteins.

Main Methods:

  • Co-immunoprecipitation and High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) were used to identify N-Myc PTMs and interacting proteins.
  • In vitro assays were performed to assess the interaction between N-Myc and p300.
  • Analysis of patient data was conducted to correlate p300 expression with NB prognosis.

Main Results:

  • 16 PTM residues and 114 potential N-Myc-interacting proteins were identified, including acetylation and ubiquitination on lysine 199.
  • The protein p300 was found to interact with N-Myc and modulate its protein stability and lysine-199 modification status.
  • p300 expression levels correlated with poor prognosis in neuroblastoma patients.

Conclusions:

  • p300 is a potential therapeutic target for treating MYCN-amplified neuroblastoma.
  • The identified PTMs and interacting proteins represent novel targets for future research in NB therapy.
  • Modulating N-Myc PTMs offers a promising avenue for developing new neuroblastoma treatments.
Keywords:
MYCNinteracting proteinsneuroblastomapost-translational modificationsprotein stability

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