Emodin potentiates the antiproliferative effect of interferon alpha/beta by activation of JAK/STAT pathway signaling through inhibition of the 26S proteasome
文献类型：期刊论文
| 作者 | Wang, F (reprint author), Chinese Acad Sci, Sichuan Translat Med Res Hosp, Chengdu, Peoples R China.; He, YJ; Huang, JM; Wang, P; Li, S; Yang, LJ; Liu, WL; Suksamrarn, A; Zhang, GL; Wang, F |
| 刊名 | ONCOTARGET
 |
| 出版日期 | 2016 |
| 卷号 | 7期号:4页码:4664-4679 |
| 关键词 | Emodin Interferon Jak/stat 26s Proteasome |
| 产权排序 | 1 |
| 文献子类 | Article |
| 英文摘要 | The 26S proteasome is a negative regulator of type I interferon (IFN-alpha/beta) signaling. Inhibition of the 26S proteasome by small molecules may be a new strategy to enhance the efficacy of type I IFNs and reduce their side effects. Using cellbased screening assay for new 26S proteasome inhibitors, we found that emodin, a natural anthraquinone, was a potent inhibitor of the human 26S proteasome. Emodin preferably inhibited the caspase-like and chymotrypsin-like activities of the human 26S proteasome and increased the ubiquitination of endogenous proteins in cells. Computational modeling showed that emodin exhibited an orientation/ conformation favorable to nucleophilic attack in the active pocket of the beta 1, beta 2, and beta 5 subunits of the 26S proteasome. Emodin increased phosphorylation of STAT1, decreased phosphorylation of STAT3 and increased endogenous gene expression stimulated by IFN-alpha. Emodin inhibited IFN-alpha-stimulated ubiquitination and degradation of type I interferon receptor 1 (IFNAR1). Emodin also sensitized the antiproliferative effect of IFN-a in HeLa cervical carcinoma cells and reduced tumor growth in Huh7 hepatocellular carcinoma-bearing mice. These results suggest that emodin potentiates the antiproliferative effect of IFN-alpha by activation of JAK/ STAT pathway signaling through inhibition of 26S proteasome-stimulated IFNAR1 degradation. Therefore, emodin warrants further investigation as a new means to enhance the efficacy of IFN-alpha/beta. |
| 学科主题 | Oncology ; Cell Biology |
| 资助项目 | 天然药物和临床转化实验室 |
| 语种 | 英语 |
| 资助机构 | National Natural Science Foundation of China [91213304, 91413108, 2151101054, 21372214] ; National Natural Science Foundation of China [91213304, 91413108, 2151101054, 21372214] ; West Light Foundation of the Chinese Academy of Sciences ; West Light Foundation of the Chinese Academy of Sciences ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; Pillar Program of Science and Technology Department of Sichuan Province [2012SZ0219] ; Pillar Program of Science and Technology Department of Sichuan Province [2012SZ0219] ; National Natural Science Foundation of China [91213304, 91413108, 2151101054, 21372214] ; National Natural Science Foundation of China [91213304, 91413108, 2151101054, 21372214] ; West Light Foundation of the Chinese Academy of Sciences ; West Light Foundation of the Chinese Academy of Sciences ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; Sichuan Youth Science & Technology Foundation [2014JQ0028] ; Pillar Program of Science and Technology Department of Sichuan Province [2012SZ0219] ; Pillar Program of Science and Technology Department of Sichuan Province [2012SZ0219] |
| 源URL | [http://210.75.237.14/handle/351003/28208]  |
| 专题 | 成都生物研究所_天然产物研究 |
| 通讯作者 | Wang, F (reprint author), Chinese Acad Sci, Sichuan Translat Med Res Hosp, Chengdu, Peoples R China.; Zhang, GL; Wang, F (reprint author), Chinese Acad Sci, Chengdu Inst Biol, Key Lab Nat Med & Clin Translat, Chengdu, Peoples R China. |
| 推荐引用方式 GB/T 7714 | Wang, F ,He, YJ,Huang, JM,et al. Emodin potentiates the antiproliferative effect of interferon alpha/beta by activation of JAK/STAT pathway signaling through inhibition of the 26S proteasome[J]. ONCOTARGET,2016,7(4):4664-4679. |
| APA | Wang, F .,He, YJ.,Huang, JM.,Wang, P.,Li, S.,...&Shen, XF.(2016).Emodin potentiates the antiproliferative effect of interferon alpha/beta by activation of JAK/STAT pathway signaling through inhibition of the 26S proteasome.ONCOTARGET,7(4),4664-4679. |
| MLA | Wang, F ,et al."Emodin potentiates the antiproliferative effect of interferon alpha/beta by activation of JAK/STAT pathway signaling through inhibition of the 26S proteasome".ONCOTARGET 7.4(2016):4664-4679. |
入库方式： OAI收割
来源：成都生物研究所
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