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Updated: Jul 29, 2025

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
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HSP90-regulated CHIP/TRIM21/p21 Axis Involves in the Senescence of Osteosarcoma Cells

Gui-Sheng Xu1,2, Yu-Ning Lin2, Qingzhong Zeng3

  • 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, Guangdong, China.

Protein and Peptide Letters
|May 22, 2023
PubMed
Abstract

Insights

Heat shock protein 90 (HSP90) stabilizes tripartite motif 21 (TRIM21) in osteosarcoma (OS). This HSP90/CHIP/TRIM21/p21 axis regulates OS cell senescence, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Osteosarcoma (OS) is a prevalent malignant bone tumor with a poor prognosis.
  • Tripartite motif 21 (TRIM21) is implicated in OS, regulating the TXNIP/p21 axis and OS cell senescence.

Purpose of the Study:

  • To investigate the molecular mechanism of TRIM21 in osteosarcoma (OS).
  • To explore the regulatory mechanism of TRIM21 protein stability during OS cell senescence.

Main Methods:

  • Co-immunoprecipitation (co-IP) to assess TRIM21 and HSP90 interaction.
  • Western blot and qRT-PCR to analyze protein and mRNA expression.
  • SA-β-gal staining to evaluate OS cell senescence.

Main Results:

  • HSP90 interacts with and stabilizes TRIM21 in OS cells.
  • HSP90 inhibition accelerates TRIM21 proteasomal degradation, mediated by CHIP E3 ligase.
  • TRIM21 inhibits OS senescence and downregulates p21; CHIP has an opposing effect on p21.

Conclusions:

  • HSP90 stabilizes TRIM21 in OS, influencing OS cell senescence.
  • The CHIP/TRIM21/p21 axis, modulated by HSP90, plays a critical role in OS senescence.
Keywords:
CHIPHSP90OsteosarcomaTRIM21p21senescence.

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