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Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation
The inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene Z...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413129/ https://www.ncbi.nlm.nih.gov/pubmed/34282274 http://dx.doi.org/10.1038/s41388-021-01949-5 |
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author | Tang, Jun Peng, Weiyan Feng, Yixiao Le, Xin Wang, Kang Xiang, Qin Li, Lili Wang, Yan Xu, Can Mu, Junhao Xu, Ke Ji, Ping Tao, Qian Huang, Ailong Deng, Chu-Xia Lin, Yong Xiang, Tingxiu |
author_facet | Tang, Jun Peng, Weiyan Feng, Yixiao Le, Xin Wang, Kang Xiang, Qin Li, Lili Wang, Yan Xu, Can Mu, Junhao Xu, Ke Ji, Ping Tao, Qian Huang, Ailong Deng, Chu-Xia Lin, Yong Xiang, Tingxiu |
author_sort | Tang, Jun |
collection | PubMed |
description | The inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene ZDHHC1 that suppresses tumor growth when the expression was restored, but the specific mechanism was yet to be found. The protein product of ZDHHC1 is an S-palmitoyltransferase and we have identified p53 as a substrate for ZDHHC1-mediated palmitoylation, specifically at the C135, C176, and C275 residues. The novel form of post-translational modification of p53 is required for the nuclear translocation of the tumor suppressor. p53 recruited DNMT3A to ZDHHC1 promoter and is responsible for the hypermethylation of ZDHHC1. The epigenetic feedback loop formed by ZDHHC1 and p53 sheds light on the inactivation of p53 without the presence of genetic mutations. |
format | Online Article Text |
id | pubmed-8413129 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84131292021-09-22 Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation Tang, Jun Peng, Weiyan Feng, Yixiao Le, Xin Wang, Kang Xiang, Qin Li, Lili Wang, Yan Xu, Can Mu, Junhao Xu, Ke Ji, Ping Tao, Qian Huang, Ailong Deng, Chu-Xia Lin, Yong Xiang, Tingxiu Oncogene Article The inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene ZDHHC1 that suppresses tumor growth when the expression was restored, but the specific mechanism was yet to be found. The protein product of ZDHHC1 is an S-palmitoyltransferase and we have identified p53 as a substrate for ZDHHC1-mediated palmitoylation, specifically at the C135, C176, and C275 residues. The novel form of post-translational modification of p53 is required for the nuclear translocation of the tumor suppressor. p53 recruited DNMT3A to ZDHHC1 promoter and is responsible for the hypermethylation of ZDHHC1. The epigenetic feedback loop formed by ZDHHC1 and p53 sheds light on the inactivation of p53 without the presence of genetic mutations. Nature Publishing Group UK 2021-07-19 2021 /pmc/articles/PMC8413129/ /pubmed/34282274 http://dx.doi.org/10.1038/s41388-021-01949-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tang, Jun Peng, Weiyan Feng, Yixiao Le, Xin Wang, Kang Xiang, Qin Li, Lili Wang, Yan Xu, Can Mu, Junhao Xu, Ke Ji, Ping Tao, Qian Huang, Ailong Deng, Chu-Xia Lin, Yong Xiang, Tingxiu Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation |
title | Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation |
title_full | Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation |
title_fullStr | Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation |
title_full_unstemmed | Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation |
title_short | Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation |
title_sort | cancer cells escape p53’s tumor suppression through ablation of zdhhc1-mediated p53 palmitoylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413129/ https://www.ncbi.nlm.nih.gov/pubmed/34282274 http://dx.doi.org/10.1038/s41388-021-01949-5 |
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