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The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis
Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses o...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Association for the Advancement of Science
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904255/ https://www.ncbi.nlm.nih.gov/pubmed/33627431 http://dx.doi.org/10.1126/sciadv.abe5518 |
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| author | Yi, Fei Zhang, Ying Wang, Zhijun Wang, Zhuo Li, Ziwei Zhou, Tingting Xu, Hongde Liu, Jingwei Jiang, Bo Li, Xiaoman Wang, Liang Bai, Ning Guo, Qiqiang Guan, Yi Feng, Yanling Mao, Zhiyong Fan, Guangjian Zhang, Shengping Wang, Chuangui Cao, Longyue O’Rourke, Brian P. Wang, Yang Wu, Yanmei Wu, Boquan You, Shilong Zhang, Naijin Guan, Junlin Song, Xiaoyu Sun, Yingxian Wei, Shi Cao, Liu |
| author_facet | Yi, Fei Zhang, Ying Wang, Zhijun Wang, Zhuo Li, Ziwei Zhou, Tingting Xu, Hongde Liu, Jingwei Jiang, Bo Li, Xiaoman Wang, Liang Bai, Ning Guo, Qiqiang Guan, Yi Feng, Yanling Mao, Zhiyong Fan, Guangjian Zhang, Shengping Wang, Chuangui Cao, Longyue O’Rourke, Brian P. Wang, Yang Wu, Yanmei Wu, Boquan You, Shilong Zhang, Naijin Guan, Junlin Song, Xiaoyu Sun, Yingxian Wei, Shi Cao, Liu |
| author_sort | Yi, Fei |
| collection | PubMed |
| description | Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs. Mass spectrometry analysis revealed that SIRT2 interacts with and deacetylates the structural maintenance of chromosomes protein 1 (SMC1A), which then promotes SMC1A phosphorylation to properly drive mitosis. We have further demonstrated that inhibition of SIRT2 activity or continuously increasing SMC1A-K579 acetylation causes abnormal chromosome segregation, which, in turn, induces mitotic catastrophe in cancer cells and enhances their vulnerability to chemotherapeutic agents. These findings suggest that regulation of the SIRT2-SMC1A axis through deacetylation-phosphorylation permits escape from mitotic catastrophe, thus allowing early precursor lesions to overcome oncogenic stress. |
| format | Online Article Text |
| id | pubmed-7904255 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-79042552021-03-10 The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis Yi, Fei Zhang, Ying Wang, Zhijun Wang, Zhuo Li, Ziwei Zhou, Tingting Xu, Hongde Liu, Jingwei Jiang, Bo Li, Xiaoman Wang, Liang Bai, Ning Guo, Qiqiang Guan, Yi Feng, Yanling Mao, Zhiyong Fan, Guangjian Zhang, Shengping Wang, Chuangui Cao, Longyue O’Rourke, Brian P. Wang, Yang Wu, Yanmei Wu, Boquan You, Shilong Zhang, Naijin Guan, Junlin Song, Xiaoyu Sun, Yingxian Wei, Shi Cao, Liu Sci Adv Research Articles Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs. Mass spectrometry analysis revealed that SIRT2 interacts with and deacetylates the structural maintenance of chromosomes protein 1 (SMC1A), which then promotes SMC1A phosphorylation to properly drive mitosis. We have further demonstrated that inhibition of SIRT2 activity or continuously increasing SMC1A-K579 acetylation causes abnormal chromosome segregation, which, in turn, induces mitotic catastrophe in cancer cells and enhances their vulnerability to chemotherapeutic agents. These findings suggest that regulation of the SIRT2-SMC1A axis through deacetylation-phosphorylation permits escape from mitotic catastrophe, thus allowing early precursor lesions to overcome oncogenic stress. American Association for the Advancement of Science 2021-02-24 /pmc/articles/PMC7904255/ /pubmed/33627431 http://dx.doi.org/10.1126/sciadv.abe5518 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
| spellingShingle | Research Articles Yi, Fei Zhang, Ying Wang, Zhijun Wang, Zhuo Li, Ziwei Zhou, Tingting Xu, Hongde Liu, Jingwei Jiang, Bo Li, Xiaoman Wang, Liang Bai, Ning Guo, Qiqiang Guan, Yi Feng, Yanling Mao, Zhiyong Fan, Guangjian Zhang, Shengping Wang, Chuangui Cao, Longyue O’Rourke, Brian P. Wang, Yang Wu, Yanmei Wu, Boquan You, Shilong Zhang, Naijin Guan, Junlin Song, Xiaoyu Sun, Yingxian Wei, Shi Cao, Liu The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis |
| title | The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis |
| title_full | The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis |
| title_fullStr | The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis |
| title_full_unstemmed | The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis |
| title_short | The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis |
| title_sort | deacetylation-phosphorylation regulation of sirt2-smc1a axis as a mechanism of antimitotic catastrophe in early tumorigenesis |
| topic | Research Articles |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904255/ https://www.ncbi.nlm.nih.gov/pubmed/33627431 http://dx.doi.org/10.1126/sciadv.abe5518 |
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