Taraxasterol acetate targets RNF31 to inhibit RNF31/p53 axis-driven cell proliferation in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that taraxasterol acetate (TA) can inhibit the growth of tumor cells. However, to date, it remains unclear how TA inhibits cell growth and how RNF31 functions as an oncogene. We examined the expression...

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Bibliographic Details
Published in:Cell death discovery 2021-04, Vol.7 (1), p.66-66, Article 66
Main Authors: Tang, Chao-Tao, Yang, Jing, Liu, Zi-De, Chen, Youxiang, Zeng, Chunyan
Format: Article
Language:English
Subjects:
631/67/1059/153
692/699/67/1504/1885/1393
Acetic acid
Apoptosis
Autophagy
Biochemistry
Biomedical and Life Sciences
Cancer
Cell Biology
Cell Cycle Analysis
Cell growth
Cell proliferation
Chloroquine
Colorectal cancer
Colorectal carcinoma
Cycloheximide
Degradation
Immunofluorescence
Immunohistochemistry
Immunoprecipitation
Life Sciences
p53 Protein
Phagocytosis
Stem Cells
Tumor cells
Ubiquitination
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Summary:Colorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that taraxasterol acetate (TA) can inhibit the growth of tumor cells. However, to date, it remains unclear how TA inhibits cell growth and how RNF31 functions as an oncogene. We examined the expression of RNF31 in CRC tissue samples via immunohistochemistry and elucidated the function of RNF31 in CRC cells by constructing a cell model with RNF31 depletion. A cycloheximide (CHX)-chase analysis and immunofluorescence assays were conducted to demonstrate that TA can promote RNF31 degradation by activating autophagy. We used the PharmMapper website to predict targets of TA and identified RNF31. CHX-chase experiments showed that TA could facilitate RNF31 degradation, which was inhibited by the administration of chloroquine. Immunofluorescence assays showed that RNF31 protein was colocalized with LC3I/II and p62, suggesting that TA promoted RNF31 degradation by activating autophagy. We also found that CRC patients with RNF31 overexpression had poorer survival than those with low RNF31 expression. The results of the CHX-chase experiment showed that depletion of RNF31 alleviated p53 degradation, which was inhibited by MG132. A series of co-immunoprecipitation (Co-IP) assays revealed that RNF31 interacts with p53 and promotes p53 ubiquitination and degradation. A Co-IP assay performed with a truncated RNF31 plasmid showed that the PUB domain interacts with p53. Moreover, the PUB domain is the key structure in the induction of p53 ubiquitination. Our findings reveal a key role of RNF31 in CRC cell growth and indicate a mechanism through which TA inhibits cell growth.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-021-00449-5