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Updated: Nov 16, 2025

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

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Ubiquitination of Nonhistone Proteins in Cancer Development and Treatment

Xiuzhen Zhang1, Tong Meng2, Shuaishuai Cui1

  • 1School of Life Sciences, Shandong University of Technology, Zibo, China.

Frontiers in Oncology
|March 1, 2021
PubMed

Insights

The ubiquitin-proteasome system (UPS) regulates key cancer processes. Targeting UPS components and using PROTACs offers novel cancer treatment strategies by modulating protein stability.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Ubiquitination is a critical post-translation modification regulating protein stability and localization.
  • The ubiquitin-proteasome system (UPS) governs essential cellular functions, including DNA repair, transcription, and apoptosis.
  • Dysregulation of the UPS is implicated in cancer development and progression.

Purpose of the Study:

  • To review the regulatory roles of UPS members on nonhistone substrates in cancer.
  • To highlight therapeutic interventions targeting UPS components.
  • To discuss the potential of proteolysis-targeting chimeras (PROTACs) in cancer therapy.

Main Methods:

  • Literature review of key UPS members and their substrates in cancer.
  • Analysis of UPS involvement in cancer-related processes (cell cycle, proliferation, apoptosis, DNA repair, inflammation, T cell dysfunction).
  • Exploration of therapeutic strategies targeting E1s, E2s, E3s, proteasomes, and deubiquitinating enzymes.

Main Results:

  • The UPS significantly impacts nonhistone protein regulation in cancer.
  • UPS dysregulation contributes to various hallmarks of cancer.
  • Novel therapeutic targets within the UPS are identified.
  • PROTACs represent a promising strategy for UPS-mediated protein degradation in cancer.

Conclusions:

  • The UPS is a critical regulator of nonhistone proteins in cancer.
  • Targeting the UPS offers a viable therapeutic avenue for cancer treatment.
  • PROTAC technology holds significant potential for developing novel anticancer therapies by leveraging the UPS.
Keywords:
E3 ligasecancerdeubiquitinasenonhistone proteinproteolysis-targeting chimerasubiquitination

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