Related Experiment Video
Updated: Aug 6, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
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.
Abstract:
Bladder cancer is a common and aggressive disease with limited treatment options, highlighting the urgent need for new therapeutic strategies. Although mitochondrial proteins have been implicated in cancer progression, their role in bladder cancer remains unclear. This study aimed to investigate the function of the mitochondrial protease YME1L1 and its regulation by the E3 ubiquitin ligase TRIM21. By analyzing patient tissue samples, single-cell RNA data and performing experiments manipulating YME1L1 and TRIM21 levels in bladder cancer cells, we found that YME1L1 promotes cancer cell proliferation, invasion and mitochondrial energy production. Mechanistically, TRIM21 interacts with YME1L1 through its SPRY domain, facilitating K63-linked polyubiquitination of YME1L1 and accelerating its degradation. Furthermore, the K237 residue of YME1L1 is critical for TRIM21-mediated ubiquitination. These findings suggest that targeting the TRIM21-YME1L1 pathway could offer a novel strategy to inhibit bladder cancer progression.
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.
Related Concept Videos
Abnormal Proliferation
Mitochondria
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...