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Updated: Sep 29, 2025

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology
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Deubiquitinase Vulnerabilities Identified through Activity-Based Protein Profiling in Non-Small Cell Lung Cancer

Shikha Mahajan, Anurima Majumder, Paul A Stewart

    ACS Chemical Biology
    |March 21, 2022
    PubMed

    Insights

    Researchers identified key deubiquitinases (DUBs) in non-small cell lung cancer (NSCLC) using activity-based protein profiling and genetic screens. This work highlights potential new drug targets for treating lung cancer subtypes.

    Area of Science:

    • Oncology
    • Biochemistry
    • Proteomics

    Background:

    • Deubiquitinases (DUBs) play crucial roles in cellular processes and are implicated in cancer development.
    • Identifying specific DUBs involved in non-small cell lung cancer (NSCLC) is essential for developing targeted therapies.

    Purpose of the Study:

    • To prioritize deubiquitinases (DUBs) as potential anticancer targets in non-small cell lung cancer (NSCLC).
    • To identify DUBs that are overexpressed or essential for the viability of NSCLC cells.

    Main Methods:

    • Combined activity-based protein profiling (ABPP) with mass spectrometry on NSCLC tumor tissues and cell lines.
    • Analyzed existing RNA interference (RNAi) and CRISPR screening data for lung cancer.
    • Utilized a COPS5/CSN5 inhibitor to investigate the role of COPS6 in lung cancer.

    Main Results:

    • Identified 67 DUBs in NSCLC tissues.
    • Found 17 DUBs overexpressed in specific NSCLC histologies (adenocarcinoma or squamous cell).
    • Highlighted 12 DUBs affecting lung cancer cell viability in genetic screens, including COPS6.

    Conclusions:

    • The study provides a valuable resource for understanding DUB signaling in lung cancer.
    • Nominates specific DUBs, such as COPS6, as druggable targets for NSCLC treatment.
    • Offers a strategic approach for prioritizing anticancer targets in specific cancer subtypes.

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