Deubiquitination and Stabilization of PD-L1 by CSN5

被引：661

作者：

Lim, Seung-Oe ^{[1
]}

Li, Chia-Wei ^{[1
]}

Xia, Weiya ^{[1
]}

Cha, Jong-Ho ^{[1
,5
]}

Chan, Li-Chuan ^{[1
,4
]}

Wu, Yun ^{[2
]}

Chang, Shih-Shin ^{[1
,4
]}

Lin, Wan-Chi ^{[1
]}

Hsu, Jung-Mao ^{[1
]}

Hsu, Yi-Hsin ^{[1
]}

Kim, Taewan ^{[1
]}

Chang, Wei-Chao ^{[6
,7
]}

Hsu, Jennifer L. ^{[1
,6
,7
]}

Yamaguchi, Hirohito ^{[1
]}

Ding, Qingqing ^{[1
]}

Wang, Yan ^{[1
]}

Yang, Yi ^{[1
]}

Chen, Chung-Hsuan ^{[9
]}

Sahin, Aysegul A. ^{[2
]}

Yu, Dihua ^{[1
,4
]}

Hortobagyi, Gabriel N. ^{[3
]}

Hung, Mien-Chie ^{[1
,4
,6
,7
,8
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Unit 108, 1515 Holcombe Blvd, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[4] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA

[5] Seoul Natl Univ, Coll Pharm, Tumor Microenvironm Global Core Res Ctr, Seoul 151742, South Korea

[6] China Med Univ, Ctr Mol Med, Taichung 404, Taiwan

[7] China Med Univ, Grad Inst Canc Biol, Taichung 404, Taiwan

[8] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan

[9] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan

来源：

CANCER CELL | 2016年 / 30卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

NF-KAPPA-B; TNF-ALPHA; INFLAMMATION; BLOCKADE; KINASE; CTLA-4; CELLS; PHOSPHORYLATION; SUPERFAMILY; INHIBITION;

D O I：

10.1016/j.ccell.2016.10.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (INF-alpha) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-kappa B p65, is required for TNF-alpha-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.

引用

页码：925 / 939

页数：15

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