Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication
Abstract p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the prote...
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2021
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oai:doaj.org-article:85907f4c3e4044ed90ab1675dff51c6d2021-12-02T13:50:17ZStabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication10.1038/s41698-021-00153-82397-768Xhttps://doaj.org/article/85907f4c3e4044ed90ab1675dff51c6d2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00153-8https://doaj.org/toc/2397-768XAbstract p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18. In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein. Loss of CYLD causes the degradation of p18 and induces the G1/S transition. Epstein–Barr virus (EBV), is the human oncovirus etiologically linked to nasopharyngeal carcinoma (NPC). Here we found that EBV drives a replication passive environment by deregulating the CYLD-p18 axis. Functionally, CYLD inhibits cell proliferation and tumorigenesis through p18 in vivo. Restoring CYLD prevents EBV induced viral replication and tumor growth. Collectively, our results identify CYLD directly stabilizes p18 to regulate the cellular G1/S transition. The reconstitution of CYLD-p18 axis could be a promising approach for EBV-positive cancer therapy.Yueshuo LiFeng ShiJianmin HuLonglong XieLin ZhaoMin TangXiangjian LuoMao YeHui ZhengMin ZhouNa LiuAnn M. BodeJia FanJian ZhouQiang GaoShuangjian QiuWeizhong WuXin ZhangWeihua LiaoYa CaoNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-14 (2021) |
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yueshuo Li Feng Shi Jianmin Hu Longlong Xie Lin Zhao Min Tang Xiangjian Luo Mao Ye Hui Zheng Min Zhou Na Liu Ann M. Bode Jia Fan Jian Zhou Qiang Gao Shuangjian Qiu Weizhong Wu Xin Zhang Weihua Liao Ya Cao Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication |
| description |
Abstract p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18. In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein. Loss of CYLD causes the degradation of p18 and induces the G1/S transition. Epstein–Barr virus (EBV), is the human oncovirus etiologically linked to nasopharyngeal carcinoma (NPC). Here we found that EBV drives a replication passive environment by deregulating the CYLD-p18 axis. Functionally, CYLD inhibits cell proliferation and tumorigenesis through p18 in vivo. Restoring CYLD prevents EBV induced viral replication and tumor growth. Collectively, our results identify CYLD directly stabilizes p18 to regulate the cellular G1/S transition. The reconstitution of CYLD-p18 axis could be a promising approach for EBV-positive cancer therapy. |
| format |
article |
| author |
Yueshuo Li Feng Shi Jianmin Hu Longlong Xie Lin Zhao Min Tang Xiangjian Luo Mao Ye Hui Zheng Min Zhou Na Liu Ann M. Bode Jia Fan Jian Zhou Qiang Gao Shuangjian Qiu Weizhong Wu Xin Zhang Weihua Liao Ya Cao |
| author_facet |
Yueshuo Li Feng Shi Jianmin Hu Longlong Xie Lin Zhao Min Tang Xiangjian Luo Mao Ye Hui Zheng Min Zhou Na Liu Ann M. Bode Jia Fan Jian Zhou Qiang Gao Shuangjian Qiu Weizhong Wu Xin Zhang Weihua Liao Ya Cao |
| author_sort |
Yueshuo Li |
| title |
Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication |
| title_short |
Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication |
| title_full |
Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication |
| title_fullStr |
Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication |
| title_full_unstemmed |
Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication |
| title_sort |
stabilization of p18 by deubiquitylase cyld is pivotal for cell cycle progression and viral replication |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/85907f4c3e4044ed90ab1675dff51c6d |
| work_keys_str_mv |
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