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Updated: Feb 14, 2026

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
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A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

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Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF

Aram Ko1, Su Yeon Han1, Chel Hun Choi2,3

  • 1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Korea.

Cell Death and Differentiation
|February 24, 2018
PubMed

Insights

Oncogene-induced senescence (OIS) is a tumor suppression mechanism. This study reveals how c-Myc stabilizes p14ARF protein via USP10, maintaining OIS and preventing cancer progression.

Area of Science:

  • Cellular senescence
  • Tumor suppression
  • Oncogene signaling

Background:

  • Oncogene-induced senescence (OIS) is a key tumor suppressor mechanism preventing cellular transformation.
  • c-Myc oncogene drives OIS by activating p14ARF and p53 pathways.
  • Post-translational regulation of p14ARF under oncogenic stress remains underexplored.

Purpose of the Study:

  • Investigate the role of post-translational modifications in c-Myc-induced OIS.
  • Elucidate the mechanism by which c-Myc regulates p14ARF stability.
  • Determine the clinical relevance of the c-Myc-USP10-p14ARF axis in cancer.

Main Methods:

  • Utilized mouse embryonic fibroblasts and human primary cells.
  • Assessed protein stability and degradation pathways.
  • Investigated gene transcription and protein deubiquitination.
  • Analyzed clinical data from non-small cell lung cancer patients.

Main Results:

  • c-Myc induces ubiquitin-specific protease 10 (USP10) transcription.
  • USP10 deubiquitinates and stabilizes p14ARF, preventing its proteasomal degradation.
  • USP10 deficiency in cells bypasses c-Myc-induced senescence, promoting hyper-proliferation and transformation.
  • Disruption of the c-Myc-USP10-p14ARF axis correlates with poor survival in lung cancer patients.

Conclusions:

  • USP10 is a critical mediator of c-Myc-induced OIS by stabilizing p14ARF.
  • The c-Myc-USP10-p14ARF pathway is essential for tumor suppression.
  • This axis represents a potential therapeutic target in cancers with disrupted OIS.

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