Proteomic identification of the oncoprotein STAT3 as a target of a novel Skp1 inhibitor
文献类型：期刊论文
| 作者 | 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 |
| 刊名 | ONCOTARGET
 |
| 出版日期 | 2017-01-10 |
| 卷号 | 8期号:2页码:2681-2693 |
| 关键词 | proteome microarray 6-O-angeloylplenolin STAT3 inhibitor Skp2 lung cancer |
| 英文摘要 | 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. |
| 类目[WOS] | Oncology ; Cell Biology |
| 研究领域[WOS] | Oncology ; Cell Biology |
| 关键词[WOS] | CELL LUNG-CANCER ; EPIDERMAL-GROWTH-FACTOR ; MITOTIC DRUG TARGETS ; GENE-EXPRESSION ; CONSTITUTIVE ACTIVATION ; SOMATIC MUTATIONS ; CENTIPEDA-MINIMA ; COLON-CANCER ; IN-VIVO ; SURVIVAL |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000391506300067 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/45639]  |
| 专题 | 昆明植物研究所_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. |
入库方式： OAI收割
来源：昆明植物研究所
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