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USP7 interacts with and destabilizes oncoprotein SET

Jianyuan Chen1, Zishan Jiao1, Yajing Liu1

  • 1State Key Laboratory of Common Mechanism Research for Major Diseases & Department of Medical Genetics, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.

Biochemical and Biophysical Research Communications
|March 31, 2024
PubMed

Insights

The study identifies ubiquitin-specific protease 7 (USP7) as a regulator of the oncoprotein SE translocation (SET). USP7 destabilizes SET protein levels, offering a new target for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The oncoprotein SE translocation (SET) is overexpressed in various cancers, correlating with poor patient prognosis.
  • Targeting SET is a promising cancer intervention strategy, but its regulatory mechanisms are unclear.
  • Understanding SET regulation is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To identify proteins that regulate the oncoprotein SET.
  • To investigate the role of ubiquitin-specific protease 7 (USP7) in SET regulation.
  • To elucidate the interaction between USP7 and SET.

Main Methods:

  • Tandem affinity purification-mass spectrometry (TAP-MS) to identify interacting proteins.
  • Co-immunoprecipitation and Western blotting to confirm protein complex formation.
  • USP7 knockdown experiments to assess effects on SET levels.

Main Results:

  • USP7 forms a stable complex with SET in cancer cells.
  • The acidic domain of SET binds USP7; USP7's catalytic and UBL domains are required for binding.
  • USP7 knockdown increases SET protein levels without affecting SET mRNA, indicating post-transcriptional regulation.
  • USP7 is identified as the first deubiquitinase (DUB) to associate with SET.

Conclusions:

  • USP7 destabilizes oncoprotein SET, likely via an indirect mechanism.
  • USP7 plays a novel regulatory role in controlling SET protein stability.
  • This interaction presents a potential new therapeutic target for cancers involving SET overexpression.
Keywords:
Protein-protein interactionSETStabilizationTandem affinity purificationUSP7

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