Related Experiment Video

Updated: Apr 8, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

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E3 Ubiquitin Ligase ITCH Enhances P53 Ubiquitination-Dependent Degradation and Drives Osteosarcoma Tumorigenesis

Jin Zeng1,2, Haibo Zhan2, Jun Xiao2

  • 1Xi'an Jiaotong University , Xi'an, China.

Molecular Cancer Research : MCR
|April 7, 2026
PubMed

Insights

Itchy E3 ubiquitin protein ligase (ITCH) is overexpressed in osteosarcoma (OS), promoting tumor growth by degrading the tumor suppressor P53. Targeting ITCH may offer a new therapeutic strategy for osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is an aggressive bone cancer with poor therapeutic outcomes.
  • E3 ubiquitin ligases regulate cancer pathways; Itchy E3 ubiquitin protein ligase (ITCH) is linked to poor prognosis in various cancers.
  • The role of ITCH in osteosarcoma development is currently unknown.

Purpose of the Study:

  • To investigate the expression and function of ITCH in osteosarcoma.
  • To elucidate the molecular mechanism by which ITCH influences osteosarcoma progression.
  • To evaluate ITCH as a potential therapeutic target for osteosarcoma.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry were used to assess ITCH expression in OS tissues.
  • In vitro and in vivo assays, including soft agar colony formation, Transwell, CCK8, wound healing, immunofluorescence, flow cytometry, and xenograft tumor models, were employed to evaluate ITCH function.
  • Proteomic analysis, Western blot, and immunoprecipitation were utilized to identify ITCH downstream targets.

Main Results:

  • ITCH was found to be aberrantly overexpressed in osteosarcoma tissues, correlating negatively with patient survival.
  • ITCH directly binds to and promotes the ubiquitination and degradation of P53.
  • Loss of P53 due to ITCH activity enhanced malignant phenotypes in osteosarcoma, while ITCH knockdown stabilized P53.

Conclusions:

  • ITCH acts as an oncogene in osteosarcoma by mediating P53 degradation.
  • The findings reveal a novel molecular mechanism involving ITCH and P53 in osteosarcoma pathogenesis.
  • ITCH represents a promising therapeutic target for osteosarcoma treatment.

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