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Updated: Mar 11, 2026

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Myc and Skp2 overexpression promotes p27 ubiquitination and degradation in Ewing Sarcoma

Yuta Kubota1, Masanori Kawano1, Ichiro Itonaga1

  • 1Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.

Plos One
|March 9, 2026
PubMed
Abstract

Insights

Myc and S-phase kinase-associated protein 2 (Skp2) drive Ewing sarcoma cell proliferation by accelerating the cell cycle. Inhibiting Myc and Skp2 halts tumor growth and offers new therapeutic targets for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Ewing sarcoma is a highly malignant bone and soft tissue cancer with limited treatment options.
  • Myc and S-phase kinase-associated protein 2 (Skp2) were identified as highly expressed in Ewing sarcoma cell lines.

Purpose of the Study:

  • To investigate the functional roles of Myc and Skp2 in driving Ewing sarcoma cell proliferation and cell cycle progression.
  • To elucidate the molecular mechanisms by which Myc and Skp2 influence cell cycle regulators.

Main Methods:

  • siRNA-mediated knockdown and overexpression of Myc and Skp2.
  • Cell proliferation, cell cycle, and protein expression analyses.
  • Immunoprecipitation, western blotting, and xenograft mouse models were used to validate findings.

Main Results:

  • Knockdown of Myc and Skp2 significantly reduced Ewing sarcoma cell growth and induced G1 cell cycle arrest.
  • Suppression of Myc and Skp2 decreased CDK2 activity, increased p27 levels, and reduced cyclin E expression.
  • Myc and Skp2 were shown to promote p27 degradation and Rb phosphorylation, impacting E2F1 activation.

Conclusions:

  • A novel mechanism involving Myc and Skp2 in accelerating the Ewing sarcoma cell cycle was uncovered.
  • These findings provide critical insights for developing targeted therapies against Ewing sarcoma.
  • The study highlights the potential for molecularly targeted treatments in a malignancy with historically poor therapeutic progress.

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