Related Experiment Video

Updated: Apr 4, 2026

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
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Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Published on: November 7, 2019

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Pan-cancer proteogenomic interrogation of the Ubiquitin Proteasome System

Tania J Gonzalez Robles1,2,3,4,5, Paul Sastourne-Haletou1,6, Maha Khan1

  • 1Division of Precision Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.

Biorxiv : the Preprint Server for Biology
|April 3, 2026
PubMed

Insights

Cancer mutations alter the Ubiquitin Proteasome System (UPS). This study identifies key E3 ubiquitin ligases and their networks, offering new therapeutic targets for cancer treatment.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Proteomics

Background:

  • The Ubiquitin Proteasome System (UPS) is crucial for protein homeostasis in both normal and cancerous cells.
  • Understanding how cancer mutations affect UPS components is vital for developing targeted therapies.
  • E3 ubiquitin ligases are key regulators within the UPS and are implicated in cancer progression.

Purpose of the Study:

  • To investigate the role of cancer driver mutations in rewiring UPS components.
  • To identify and characterize E3 ubiquitin ligases that are clinically actionable in cancer.
  • To provide a comprehensive resource for exploring UPS alterations in a pan-cancer context.

Main Methods:

  • Integrated proteogenomic analysis of UPS components across diverse tissues and cancer types.
  • Utilized harmonized multiomic datasets for comprehensive mapping.
  • Developed UbiDash, an interactive platform for data visualization and exploration.

Main Results:

  • Identified significant changes in UPS protein levels associated with specific mutations.
  • Discovered clinically actionable E3 ubiquitin ligases based on recurrent alterations, tissue-specific expression, and prognostic significance.
  • Characterized E3 regulatory networks through co-expression, co-dependency, and protein-protein interaction analyses.

Conclusions:

  • This study pinpoints clinically relevant E3 ubiquitin ligases and mutation-defined dependencies within the UPS.
  • The findings provide valuable mechanistic insights and aid in prioritizing UPS components for cancer therapy development.
  • UbiDash serves as a crucial resource for researchers studying UPS alterations in cancer.
Keywords:
E3 ubiquitin ligases (E3s)TP53TRIM28UBR5pQTLpancancerprotein degradationproteogenomicssomatic mutationsubiquitinubiquitin proteasome system

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