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Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53

Hua Lu1, Zhihui Tan1, Hyunmin Ko1

  • 1Tulane University.

Research Square
|January 23, 2024
PubMed

Insights

Tripartite motif-containing protein 26 (TRIM26) promotes colorectal cancer (CRC) by destabilizing the tumor suppressor p53. This E3 ubiquitin ligase enhances CRC cell proliferation and tumor growth, suggesting TRIM26 as a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase with known roles in various cancers.
  • The specific role of TRIM26 in colorectal cancer (CRC) and its interaction with the tumor suppressor p53 remain incompletely understood.

Approach:

  • Investigated TRIM26 and p53 interaction in CRC cells using biochemical assays, cell-based experiments, and xenograft models.
  • Analyzed TRIM26 expression in human CRC tissues via TCGA database.
  • Performed biochemical analyses to elucidate the mechanism of TRIM26-mediated p53 regulation.

Key Points:

  • Overexpression of TRIM26 enhanced CRC cell proliferation and colony formation, while its knockdown suppressed these effects.
  • TRIM26 directly binds to the C-terminus of p53, promoting its ubiquitination, degradation, and reduced activity, independent of MDM2.
  • TRIM26 also enhances MDM2-mediated p53 ubiquitination by interacting with MDM2.

Conclusions:

  • TRIM26 exhibits oncogenic potential in CRC by inhibiting p53 function through ubiquitin ligase activity.
  • TRIM26 destabilizes p53, leading to increased CRC cell proliferation and tumor growth.
  • TRIM26 represents a potential therapeutic target for colorectal cancer treatment.
Keywords:
MDM2TRIM26colorectal cancerp53tumor growthubiquitin ligase

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