| Proteomic identification of the oncoprotein STAT3 as a target of a novel Skp1 inhibitor | |
| Cheng, Xin1; Liu, Yong-Qiang1; Wang, Gui-Zhen1; Yang, Li-Na2; Lu, Yong-Zhi; Li, Xin-Chun1; Zhou, Bo1; Qu, Li-Wei1; Wang, Xiao-Lu1; Cheng, Yong-Xian3,4; Liu, Jinsong3; Tao, Sheng-Ce2; Zhou, Guang-Biao1 | |
| 2017-01-10 | |
| 发表期刊 | ONCOTARGET
 |
| 卷号 | 8期号:2页码:2681-2693 |
| 摘要 | The S phase kinase- associated protein 1 (Skp1), an adaptor protein of the Skp1-Cul1-F-box protein complex, binds the ubiquitin E3 ligase Skp2 and is critical to its biological functions. Targeting of Skp1 by a small compound 6-O-angeloylplenolin (6-OAP) results in dissociation and degradation of Skp2 and mitotic arrest of lung cancer cells. Here, by using a proteome microarray containing 16,368 proteins and a biotinylated 6-OAP, we identified 99 proteins that could bind 6-OAP, with Skp1 and STAT3 sitting at the central position of the 6-OAP interactome. 6-OAP formed hydrogen bonds with Ser611/Ser613/Arg609 at the SH2 domain of STAT3 and inhibited the constitutive and interleukin-6-induced phosphorylated STAT3 (pSTAT3), leading to inhibitory effects on lung cancer cells and suppression of Skp2 transcription. STAT3 was overexpressed in tumor samples compared to counterpart normal lung tissues and was inversely associated with prognosis of the patients. 6-OAP inhibited tumor growth in SCID mice intravenously injected with lung cancer cells, and downregulated both STAT3 and Skp2 in tumor samples. Given that 6-OAP is a Skp1 inhibitor, our data suggest that this compound may target Skp1 and STAT3 to suppress Skp2, augmenting its anti-lung cancer activity. |
| 关键词 | Proteome Microarray 6-o-angeloylplenolin Stat3 Inhibitor Skp2 Lung Cancer |
| DOI | 10.18632/oncotarget.13153 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000391506300067 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/45639 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Div Mol Carcinogenesis & Targeted Therapy Canc, Beijing 100101, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Key Lab Syst Biomed, Minist Educ, Shanghai 200240, Peoples R China 3.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China 4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Xin,Liu, Yong-Qiang,Wang, Gui-Zhen,et al. Proteomic identification of the oncoprotein STAT3 as a target of a novel Skp1 inhibitor[J]. ONCOTARGET,2017,8(2):2681-2693. |
| APA | Cheng, Xin.,Liu, Yong-Qiang.,Wang, Gui-Zhen.,Yang, Li-Na.,Lu, Yong-Zhi.,...&Zhou, Guang-Biao.(2017).Proteomic identification of the oncoprotein STAT3 as a target of a novel Skp1 inhibitor.ONCOTARGET,8(2),2681-2693. |
| MLA | Cheng, Xin,et al."Proteomic identification of the oncoprotein STAT3 as a target of a novel Skp1 inhibitor".ONCOTARGET 8.2(2017):2681-2693. |
| 条目包含的文件 | 下载所有文件 | |||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| oncotarget-08-2681.p（7649KB） | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | 浏览 下载 | |
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
修改评论