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Updated: Jul 18, 2025

Techniques to Induce and Quantify Cellular Senescence
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Techniques to Induce and Quantify Cellular Senescence

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USP13 regulates cell senescence through mediating MDM2 stability

Jinshan He1, Boina Baoyinna2, Sarah J Taleb2

  • 1Department of Physiology and Cell Biology, the Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, the Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

Life Sciences
|August 27, 2023
PubMed
Abstract

Insights

Ubiquitin-Specific Protease 13 (USP13) promotes lung cell senescence and aging by reducing MDM2 levels. This deubiquitinating enzyme plays a key role in lung aging mechanisms.

Area of Science:

  • Gerontology
  • Molecular Biology
  • Cellular Biology

Background:

  • Lung aging impairs function, remodeling, and regeneration, increasing disease susceptibility.
  • Deubiquitinating enzymes (DUBs) are implicated in aging and disease via cellular signaling.
  • The specific role of Ubiquitin-Specific Protease 13 (USP13) in lung aging is not well understood.

Purpose of the Study:

  • To investigate the function of USP13 in cellular senescence and lung aging.
  • To elucidate the molecular mechanisms by which USP13 influences lung aging.

Main Methods:

  • Compared USP13 and MDM2 protein levels in aged and young mouse lung tissues.
  • Utilized gene silencing and overexpression of USP13 in human cell lines.
  • Assessed MDM2 levels via qPCR and Western blotting; measured senescence using β-galactosidase staining.

Main Results:

  • Aged mouse lungs exhibited higher USP13 levels, negatively correlating with MDM2.
  • USP13 deficiency increased MDM2 levels; USP13 overexpression promoted senescence and reduced MDM2.
  • USP13 targets MDM2 for degradation, reducing its K63-linked polyubiquitination.

Conclusions:

  • USP13 is upregulated in aged lungs and promotes cellular senescence.
  • USP13 regulates lung aging pathways by controlling MDM2 protein stability.
  • USP13 represents a potential therapeutic target for age-related lung diseases.
Keywords:
Cell senescenceDeubiquitinationLung agingMDM2USP13

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