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

Zhihui Tan1,2, Hyun Min Ko1, Parnian Naji3

  • 1Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, 70112, USA.

Cell Death and Differentiation
|February 24, 2025
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:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase with varied roles in cancer.
  • The tumor suppressor protein p53 is critical in preventing cancer development.
  • Understanding TRIM26's interaction with p53 is crucial for colorectal cancer (CRC) research.

Purpose of the Study:

  • To investigate the interaction between TRIM26 and p53 in colorectal cancer (CRC) cells.
  • To elucidate the role of TRIM26 in CRC proliferation and tumor growth.
  • To determine if TRIM26 could be a potential therapeutic target for CRC.

Main Methods:

  • Biochemical assays
  • Cell-based assays
  • Xenograft experiments
  • TCGA database analysis

Main Results:

  • TRIM26 overexpression enhanced CRC cell proliferation and colony formation.
  • TRIM26 knockdown suppressed CRC cell proliferation and colony formation.
  • TRIM26 directly bound to p53, facilitating its ubiquitination, degradation, and reduced activity.
  • TRIM26 enhanced MDM2-mediated p53 ubiquitination.
  • TRIM26 is highly expressed in human CRC tissues.

Conclusions:

  • TRIM26 exhibits oncogenic potential in CRC by inhibiting p53 function.
  • TRIM26 destabilizes p53 through its ubiquitin ligase activity, promoting CRC cell proliferation and tumor growth.
  • TRIM26 represents a potential therapeutic target for CRC treatment.

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