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
Source PublicationONCOTARGET
AbstractThe 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.
KeywordProteome Microarray 6-o-angeloylplenolin Stat3 Inhibitor Skp2 Lung Cancer
Indexed BySCI
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000391506300067
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Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.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
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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.
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