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Updated: Jan 20, 2026
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Therapeutic potential of ReACp53 targeting mutant p53 protein in CRPC
Yaqun Zhang1, Lingfan Xu2,3, Yan Chang2,4
1Department of Urology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Backgrounds:
p53 is a tumor suppressor that prevents cancer onset and progression, and mutations in the p53 gene cause loss of the tumor suppressor function of the protein. The mutant p53 protein in tumor cells can form aggregates which contribute to the dominant-negative effect over the wild-type p53 protein, causing loss of p53 tumor suppression or gain of novel oncogenic functions. Mutations in p53 have been implicated in the pathogenesis of primary prostate cancer (PCa), and are often detected in recurrent and metastatic disease. Thus, targeting mutant p53 may constitute an alternative therapeutic strategy for advanced PCa for which there are no other viable options.
Methods:
In this study, we used immunoprecipitation, immunofluorescence, clonogenic survival, and cell proliferation assays, flow cytometric analysis and in vivo xenograft to investigate the biological effects of ReACp53, a cell-permeable peptide inhibitor of p53 aggregation, on mutant p53-carrying PCa cells.
Results:
Our results show that ReACp53 targets amyloid aggregates of mutant p53 protein and restores the p53 nuclear function as transcriptional factor, induces mitochondrial cell death and reduces DNA synthesis of mutant p53-carrying PCa cells; ReACp53 also inhibits xenograft tumor growth in vivo.
Conclusions:
The data presented here suggest a therapeutic potential of targeting mutant p53 protein in advanced PCa setting, which has a clinical impact for aggressive PCa with transforming how such tumors are managed.
Insights
A novel peptide inhibitor, ReACp53, targets mutant p53 aggregates in prostate cancer (PCa) cells. This restores p53 function, induces cancer cell death, and inhibits tumor growth, offering a new therapeutic strategy for advanced PCa.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Mutations in the p53 tumor suppressor gene are common in prostate cancer (PCa), leading to loss of function and promoting tumor progression.
- Mutant p53 proteins can form aggregates, contributing to dominant-negative effects and oncogenic functions, particularly in advanced and metastatic PCa.
- Targeting mutant p53 presents a potential therapeutic strategy for advanced PCa, addressing a critical unmet need.
Purpose of the Study:
- To investigate the biological effects of ReACp53, a peptide inhibitor of p53 aggregation, on PCa cells harboring mutant p53.
- To evaluate ReACp53's efficacy in restoring wild-type p53 function and its impact on cancer cell viability and proliferation.
Main Methods:
- Immunoprecipitation and immunofluorescence assays were used to analyze p53 aggregation and localization.
- Clonogenic survival and cell proliferation assays assessed the impact of ReACp53 on PCa cell growth.
- Flow cytometry and in vivo xenograft models were employed to evaluate ReACp53's effects on cell death and tumor growth.
Main Results:
- ReACp53 effectively targets and disrupts amyloid aggregates of mutant p53 protein in PCa cells.
- Treatment with ReACp53 restored the nuclear function of p53 as a transcriptional factor.
- ReACp53 induced mitochondrial cell death, reduced DNA synthesis in mutant p53-expressing PCa cells, and inhibited tumor growth in vivo.
Conclusions:
- Targeting mutant p53 aggregates with ReACp53 demonstrates significant therapeutic potential for advanced prostate cancer.
- This approach offers a promising strategy for managing aggressive PCa, potentially transforming current treatment paradigms.
- Restoring p53 tumor suppressor function by inhibiting its aggregation is a viable therapeutic avenue for PCa.
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