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Updated: Dec 20, 2025

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells
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siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells

Published on: May 24, 2014

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USP37 promotes deubiquitination of HIF2α in kidney cancer

Kai Hong1,2, Lianxin Hu3, Xijuan Liu2

  • 1Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei Province, China.

Proceedings of the National Academy of Sciences of the United States of America
|May 29, 2020
PubMed

Insights

Ubiquitin-specific peptidase 37 (USP37) stabilizes the oncogenic factor HIF2α in clear cell renal cell carcinoma (ccRCC). Inhibiting USP37 reduces tumor growth and metastasis, suggesting USP37 as a potential ccRCC therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) is linked to Von Hippel Lindau (VHL) tumor suppressor loss, causing hypoxia-inducible factor α (HIFα) accumulation.
  • HIF2α is a key oncogenic driver in ccRCC, but effective therapeutic targets are limited.

Purpose of the Study:

  • To identify deubiquitinases (DUBs) that interact with and regulate HIF2α.
  • To investigate the role of USP37 in ccRCC pathogenesis and its potential as a therapeutic target.

Main Methods:

  • A complementary DNA (cDNA) library screen was used to identify DUBs binding HIF2α.
  • USP37's enzymatic activity and effect on HIF2α stability were assessed.
  • Cell proliferation assays (MTS, colony formation) and an orthotopic xenograft model were employed.

Main Results:

  • USP37 was identified as a DUB that binds and deubiquitinates HIF2α, enhancing its protein stability.
  • USP37 depletion led to HIF2α down-regulation and reduced ccRCC cell proliferation and tumor growth.
  • Inhibition of USP37 decreased primary kidney tumor formation and lung metastasis in vivo.

Conclusions:

  • USP37 promotes ccRCC progression by stabilizing HIF2α.
  • USP37 represents a promising therapeutic target for ccRCC treatment.
Keywords:
HIF2αUSP37ccRCCdeubiquitination

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