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Deubiquitylation and stabilization of ARMC5 by ubiquitin-specific processing protease 7 (USP7) are critical for RCC

Guobei Yan1, Na Liu2, Jun Tian3

  • 1Department of Laboratory, The Second People's Hospital of Jiaozuo, the First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, China.

Journal of Cellular and Molecular Medicine
|February 5, 2021
PubMed

Insights

The deubiquitinase USP7 stabilizes the tumor suppressor ARMC5, impacting renal cancer cell proliferation. This study reveals USP7

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The ubiquitin-proteasome system regulates ARMC5, a tumor suppressor involved in meningiomas and adrenocortical tumorigenesis.
  • The deubiquitination mechanism of ARMC5 remains unclear, despite its role in cancer suppression.

Purpose of the Study:

  • To investigate the deubiquitinase responsible for ARMC5 regulation.
  • To elucidate the role of USP7 in renal cell carcinoma (RCC) proliferation via ARMC5 modulation.

Main Methods:

  • Western blot analysis to assess ARMC5 expression in renal cancer cells.
  • Screening of a deubiquitinase library to identify ARMC5-interacting enzymes.
  • In vivo and in vitro interaction assays between USP7 and ARMC5.
  • Overexpression and knockdown assays to evaluate USP7's effect on ARMC5 stability and ubiquitination.
  • Cell cycle analysis and proliferation assays.

Main Results:

  • ARMC5 expression was found to be decreased in renal cancer tissues and cell lines.
  • USP7 was identified as a deubiquitinase interacting with ARMC5.
  • USP7 increased ARMC5 protein stability by deubiquitinating it, thereby regulating ARMC5 ubiquitination.
  • USP7 modulated ARMC5 levels, affecting cell cycle progression (G1/S phases) and renal cancer cell proliferation.

Conclusions:

  • USP7 plays a significant role in renal cell carcinoma (RCC) proliferation by stabilizing ARMC5.
  • USP7-mediated regulation of ARMC5 stability is a key mechanism influencing cancer cell growth.
Keywords:
ARMC5USP7proliferationrenal cell carcinoma

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