USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1.
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1.
复制标题
USP5 通过稳定 PD-L1 促进非小细胞肺癌进展
DOI：
10.1038/s41419-021-04356-6
复制
发表时间：
2021-11-05
影响因子：
9
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Pan J;Qiao Y;Chen C;Zang H;Zhang X;Qi F;Chang C;Yang F;Sun M;Lin S;Tang Q;Li L;Wang M;Wu M;Liu Y;Lai C;Chen J;Chen G
PD-L1（CD 274）是一种免疫抑制分子，具有免疫逃逸功能，是肿瘤免疫治疗的主要靶点之一。了解控制PD-L1蛋白表达的调控机制对于指导免疫检查点阻断治疗非常重要。在这里，我们发现泛素特异性肽酶5（USP 5）是非小细胞肺癌（NSCLC）细胞中的一种新型PD-L1去泛素酶。USP 5直接与PD-L1相互作用并使PD-L1去泛素化，因此增强PD-L1蛋白的稳定性。同时，NSCLC组织中USP 5蛋白水平高度升高，与PD-L1水平呈正相关，与患者预后不良密切相关。此外，在刘易斯肺癌小鼠模型中，USP 5的敲低延缓了肿瘤生长。因此，我们确定USP 5是PD-L1的新调节因子，靶向USP 5是一种有前途的癌症治疗策略。
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.
登录
查看更多内容
影响因子：
16.6
作者：
Sato H;Niimi A;Yasuhara T;Permata TBM;Hagiwara Y;Isono M;Nuryadi E;Sekine R;Oike T;Kakoti S;Yoshimoto Y;Held KD;Suzuki Y;Kono K;Miyagawa K;Nakano T;Shibata A
通讯作者：
Shibata A
影响因子：
15.9
作者：
Chen, Guo;Magis, Andrew T.;Deng, Xingming
通讯作者：
Deng, Xingming
USP22 去泛素化 CD274 以抑制抗癌免疫
影响因子：
10.1
作者：
Huang, Xing;Zhang, Qi;Bai, Xueli
通讯作者：
Bai, Xueli
影响因子：
50.3
作者：
Lee, Heng-Huan;Wang, Ying-Nai;Hung, Mien-Chie
通讯作者：
Hung, Mien-Chie
影响因子：
50.3
作者：
Lim SO;Li CW;Xia W;Cha JH;Chan LC;Wu Y;Chang SS;Lin WC;Hsu JM;Hsu YH;Kim T;Chang WC;Hsu JL;Yamaguchi H;Ding Q;Wang Y;Yang Y;Chen CH;Sahin AA;Yu D;Hortobagyi GN;Hung MC
通讯作者：
Hung MC