YME1L1 degradation by TRIM21 inhibits bladder cancer proliferation, metastasis, and mitochondrial function

Long Sun1, Yao Yao1, Shiwei Gong1

  • 1The Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, PR China.

Oncogene
|July 20, 2026
PubMed

Insights

Mitochondrial protease YME1-like 1 (YME1L1) drives bladder cancer growth and invasion. The E3 ubiquitin ligase TRIM21 targets YME1L1 for degradation, suggesting a new therapeutic target for bladder cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Mitochondrial Biology

Background:

  • Bladder cancer necessitates novel therapeutic strategies due to its aggressive nature and limited treatment options.
  • Mitochondrial proteins are implicated in cancer, but their specific roles in bladder cancer are not fully understood.

Purpose of the Study:

  • To investigate the function of the mitochondrial protease YME1-like 1 (YME1L1) in bladder cancer.
  • To elucidate the regulatory mechanism of YME1L1 by the E3 ubiquitin ligase TRIM21.

Main Methods:

  • Analysis of patient bladder cancer tissue samples.
  • Examination of single-cell RNA sequencing data.
  • Experimental manipulation of YME1L1 and TRIM21 expression in bladder cancer cell lines.

Main Results:

  • YME1-like 1 (YME1L1) overexpression correlates with increased bladder cancer cell proliferation, invasion, and mitochondrial energy production.
  • TRIM21 interacts with YME1L1 via its SPRY domain, promoting K63-linked polyubiquitination and subsequent degradation.
  • The K237 residue on YME1L1 is essential for TRIM21-mediated ubiquitination and degradation.

Conclusions:

  • YME1-like 1 (YME1L1) is a key driver of bladder cancer progression.
  • The TRIM21-YME1L1 axis represents a potential therapeutic target for inhibiting bladder cancer.
  • Targeting the TRIM21-YME1L1 pathway may offer a novel strategy for bladder cancer treatment.

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