USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1
Abstract PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune check...
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Nature Publishing Group
2021
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oai:doaj.org-article:29b5d099a3ad4c68a7d6f7b7a805a2b52021-11-07T12:05:30ZUSP5 facilitates non-small cell lung cancer progression through stabilization of PD-L110.1038/s41419-021-04356-62041-4889https://doaj.org/article/29b5d099a3ad4c68a7d6f7b7a805a2b52021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04356-6https://doaj.org/toc/2041-4889Abstract PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.Jinghua PanYiting QiaoCongcong ChenHongjing ZangXiaojing ZhangFeng QiCunjie ChangFan YangMengqing SunShengbin LinQuandong TangLina LiMenglan WangMinjie WuYongzhu LiuCaiyong LaiJianxiang ChenGuo ChenNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-8 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Cytology QH573-671 |
| spellingShingle |
Cytology QH573-671 Jinghua Pan Yiting Qiao Congcong Chen Hongjing Zang Xiaojing Zhang Feng Qi Cunjie Chang Fan Yang Mengqing Sun Shengbin Lin Quandong Tang Lina Li Menglan Wang Minjie Wu Yongzhu Liu Caiyong Lai Jianxiang Chen Guo Chen USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1 |
| description |
Abstract PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy. |
| format |
article |
| author |
Jinghua Pan Yiting Qiao Congcong Chen Hongjing Zang Xiaojing Zhang Feng Qi Cunjie Chang Fan Yang Mengqing Sun Shengbin Lin Quandong Tang Lina Li Menglan Wang Minjie Wu Yongzhu Liu Caiyong Lai Jianxiang Chen Guo Chen |
| author_facet |
Jinghua Pan Yiting Qiao Congcong Chen Hongjing Zang Xiaojing Zhang Feng Qi Cunjie Chang Fan Yang Mengqing Sun Shengbin Lin Quandong Tang Lina Li Menglan Wang Minjie Wu Yongzhu Liu Caiyong Lai Jianxiang Chen Guo Chen |
| author_sort |
Jinghua Pan |
| title |
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1 |
| title_short |
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1 |
| title_full |
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1 |
| title_fullStr |
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1 |
| title_full_unstemmed |
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1 |
| title_sort |
usp5 facilitates non-small cell lung cancer progression through stabilization of pd-l1 |
| publisher |
Nature Publishing Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/29b5d099a3ad4c68a7d6f7b7a805a2b5 |
| work_keys_str_mv |
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| _version_ |
1718443535533867008 |