Related Experiment Video

Updated: Jul 1, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Ubiquitin-specific Peptidase 53 Suppresses Head/Neck Tumorigenesis by Stabilizing FBXW7

Min-Hong Wang1, Mei-Ren Pan2, Yu-Hsuan Hung3

  • 1Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.

Anticancer Research
|June 29, 2026
PubMed
Abstract

Insights

Ubiquitin-specific peptidase 53 (USP53) acts as a tumor suppressor in head and neck squamous cell carcinoma (HNSC). Lower USP53 levels increase proliferation and sensitivity to cyclin-dependent kinase inhibitors, revealing a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Head and neck squamous cell carcinoma (HNSC) has a poor prognosis despite current treatments.
  • Identifying novel therapeutic targets is crucial for improving HNSC patient outcomes.

Purpose of the Study:

  • To identify and experimentally validate novel prognostic factors and therapeutic targets in HNSC.
  • To investigate the role of Ubiquitin-specific peptidase 53 (USP53) in HNSC progression and treatment response.

Main Methods:

  • Bioinformatic analyses using UALCAN, cBioPortal, Reactome, L2S2, and TIMER3.
  • Experimental validation in the FaDu HNSC cell line, including proliferation, cell cycle, and sphere formation assays.
  • Proximity ligation assays to confirm protein interactions and multiomic analyses.

Main Results:

  • USP53 was identified as a downregulated gene in HNSC, correlating with a better prognosis.
  • USP53 knockdown enhanced HNSC proliferation and sensitivity to cyclin-dependent kinase inhibitors (CDKi).
  • USP53 was found to stabilize FBXW7, suppressing HNSC proliferation and negatively associating with M2 macrophages.

Conclusions:

  • USP53 functions as a tumor suppressor in HNSC by stabilizing FBXW7, impacting cell-cycle regulation.
  • This mechanism highlights a targetable vulnerability to CDKi and links deubiquitinase activity to tumor immunity.
Keywords:
FBXW7HNSCUSP53milciclib

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