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The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein

Dian Zhang1, Jiawen Li1, Chao Zhang1

  • 1Department of Thoracic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Xigong District, Luoyang, China.

Open Life Sciences
|August 19, 2024
PubMed

Insights

Researchers identified Ubiquitin-Specific Protease 35 (USP35) as a key regulator of NRF2 in esophageal cancer. USP35 deubiquitinates NRF2, impacting chemotherapy resistance and offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer chemotherapy resistance leads to poor patient outcomes.
  • The transcription factor NRF2 promotes cell survival and chemotherapy resistance.
  • NRF2 activity is regulated by ubiquitination, but the specific deubiquitinase in esophageal cancer is unknown.

Purpose of the Study:

  • To identify novel regulators of NRF2 in esophageal carcinoma.
  • To elucidate the mechanism by which NRF2 stability is controlled.
  • To explore the therapeutic potential of targeting the NRF2 pathway.

Main Methods:

  • Investigated the role of Ubiquitin-Specific Protease 35 (USP35) in NRF2 regulation.
  • Utilized biochemical assays to demonstrate USP35-mediated deubiquitination of NRF2.
  • Performed USP35 knockdown experiments in esophageal cancer cells.

Main Results:

  • Identified USP35 as a novel regulator of NRF2 stability.
  • USP35 directly interacts with NRF2 and removes ubiquitin chains.
  • Knockdown of USP35 increases NRF2 levels and enhances chemotherapy sensitivity.

Conclusions:

  • The USP35-NRF2 axis is a critical regulator in esophageal cancer.
  • USP35 deubiquitinase activity influences NRF2 stability and chemotherapy response.
  • Targeting USP35 may represent a novel therapeutic strategy for esophageal carcinoma.
Keywords:
NRF2USP35chemoresistancedeubiquitylationesophageal cancer

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