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Updated: Oct 31, 2025

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
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Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

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Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy

Xiao-Xin Sun1, Yanping Li1, Rosalie C Sears1

  • 1Department of Molecular & Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States.

Frontiers in Oncology
|June 28, 2021
PubMed

Insights

Dysregulated MYC protein levels drive cancer. Posttranslational modifications, including ubiquitination and SUMOylation, control MYC stability. Targeting these MYC regulators offers potential cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MYC oncoprotein deregulation is a key driver of tumor growth and progression.
  • MYC protein has a short half-life and is tightly regulated by posttranslational modifications.
  • Ubiquitination and SUMOylation are critical regulatory pathways influencing MYC stability and activity.

Purpose of the Study:

  • To summarize current knowledge on MYC ubiquitination.
  • To review the role of SUMOylation in MYC regulation.
  • To explore MYC ubiquitination and SUMOylation as potential therapeutic targets in cancer.

Main Methods:

  • Literature review of studies on MYC posttranslational modifications.
  • Analysis of the interplay between ubiquitination and SUMOylation pathways concerning MYC.
  • Synthesis of current findings on MYC regulation.

Main Results:

  • Ubiquitination dynamically controls MYC levels and activity during normal cellular processes.
  • Disruption of the ubiquitination/deubiquitination balance leads to MYC stabilization and activation.
  • SUMOylation interacts with ubiquitination to modulate MYC protein stability and function.

Conclusions:

  • MYC ubiquitination and SUMOylation are crucial for regulating MYC protein.
  • Aberrant regulation of these pathways contributes to cancer development.
  • Targeting MYC ubiquitination and SUMOylation pathways presents a promising therapeutic strategy for cancer treatment.
Keywords:
MYCSUMO-specific proteaseSUMOylationdeubiquitinating enzymedeubiquitinationprotein stabilityubiquitin ligaseubiquitination

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