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Published on: December 30, 2025
RING finger protein 31 promotes p53 degradation in breast cancer cells
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Abstract:
The atypical E3 ubiquitin ligase RNF31 is highly expressed in human breast cancer, the most frequent neoplastic lethality among women. Here, RNF31 depletion in breast cancer cells in combination with global gene expression profiling revealed p53 (TP53) signaling as a potential RNF31 target. Interestingly, RNF31 decreased p53 stability, whereas depletion of RNF31 in breast cancer cells caused cell cycle arrest and cisplatin-induced apoptosis in a p53-dependent manner. Furthermore, RNF31 associated with the p53/MDM2 complex and facilitated p53 polyubiquitination and degradation by stabilizing MDM2, suggesting a molecular mechanism by which RNF31 regulates cell death. Analysis of publically available clinical data sets displayed a negative correlation between RNF31 and p53 target genes, including IGFBP3 and BTG1, consistent with RNF31 regulating p53 function in vivo as well. Together, our findings suggest RNF31 as a potential therapeutic target to restore p53 function in breast cancer.
Insights
RNF31, a protein elevated in breast cancer, destabilizes the tumor suppressor p53. Inhibiting RNF31 restores p53 activity, promoting cancer cell death and suggesting RNF31 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- RNF31 (Ring Finger Protein 31) is an atypical E3 ubiquitin ligase.
- Elevated RNF31 expression is observed in human breast cancer.
- The role of RNF31 in breast cancer pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of RNF31 in breast cancer.
- To identify potential RNF31 targets in breast cancer cells.
- To elucidate the molecular mechanism by which RNF31 regulates cancer cell survival and death.
Main Methods:
- RNF31 depletion in breast cancer cells.
- Global gene expression profiling.
- Analysis of p53/MDM2 complex formation and protein stability.
- Assessment of cell cycle progression and apoptosis.
- Correlation analysis with clinical datasets.
Main Results:
- RNF31 depletion revealed p53 signaling as a target.
- RNF31 decreases p53 stability by stabilizing MDM2, promoting p53 polyubiquitination and degradation.
- RNF31 inhibition leads to p53-dependent cell cycle arrest and cisplatin-induced apoptosis.
- Clinical data show a negative correlation between RNF31 and p53 target genes (e.g., IGFBP3, BTG1).
Conclusions:
- RNF31 regulates breast cancer cell death through p53 degradation.
- RNF31 acts as an oncoprotein by inhibiting the tumor suppressor p53.
- RNF31 represents a potential therapeutic target for restoring p53 function in breast cancer.
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