Targeting of AML1-ETO in t(8;21) Leukemia by Oridonin Generates a Tumor Suppressor-Like Protein
文献类型：期刊论文
| 作者 | Zhen, Tao1,2; Wu, Chuan-Feng1,2; Liu, Ping1,2; Wu, Hai-Yan3; Zhou, Guang-Biao4; Lu, Ying1,2; Liu, Jian-Xiang1,2; Liang, Yang1,2; Li, Keqin Kathy1,2; Wang, Yue-Ying1,2 |
| 刊名 | SCIENCE TRANSLATIONAL MEDICINE
 |
| 出版日期 | 2012-03-28 |
| 卷号 | 4期号:127 |
| ISSN号 | 1946-6234 |
| DOI | 10.1126/scitranslmed.3003562 |
| 文献子类 | Article |
| 英文摘要 | Nearly 60% of acute myeloid leukemia (AML) patients with the t(8; 21)(q22; q22) translocation fail to achieve longterm disease-free survival. Our previous studies demonstrated that oridonin selectively induces apoptosis of t(8; 21) leukemia cells and causes cleavage of AML1-ETO oncoprotein resulting from t(8; 21), but the underlying mechanisms remain unclear. We show that oridonin interacted with glutathione and thioredoxin/thioredoxin reductase to increase intracellular reactive oxygen species, which in turn activated caspase-3 in t(8; 21) cells. Moreover, oridonin bound AML1-ETO, directing the enzymatic cleavage at aspartic acid 188 via caspase-3 to generate a truncated AML1-ETO (DAML1-ETO) and preventing the protein from further proteolysis. DAML1-ETO interacted with AML1-ETO and interfered with the trans-regulatory functions of remaining AML1-ETO oncoprotein, thus acting as a tumor suppressor that mediates the anti-leukemia effect of oridonin. Furthermore, oridonin inhibited the activity of c-Kit+ leukemia-initiating cells. Therefore, oridonin is a potential lead compound for molecular target-based therapy of leukemia. |
| WOS关键词 | ACUTE MYELOID-LEUKEMIA ; COLORECTAL-CANCER CELLS ; FUSION PROTEIN ; HEMATOPOIETIC STEM ; KAPPA-B ; APOPTOSIS ; EXPRESSION ; THIOREDOXIN ; THERAPY ; LEUKEMOGENESIS |
| 资助项目 | Mega project of Ministry of Science and Technology[2008ZX09312-026] ; Chinese National Key Basic Research Project (973)[2010CB529200] ; National Natural Science Foundation of China[30821063] ; National Natural Science Foundation of China[30830119] ; National Natural Science Foundation of China[81170506] ; Samuel Waxman Cancer Research Foundation CoPI[00000000] ; Knowledge Innovation Program of the Chinese Academy of Sciences[KSCX1-YW-R-26] ; Knowledge Innovation Program of the Chinese Academy of Sciences[KSCX2-YW-R-235] |
| WOS研究方向 | Cell Biology ; Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000302213400007 |
| 出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278146]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Chen, Sai-Juan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, State Key Lab Med Genom, Shanghai 200025, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China; 3.SJTU, Shanghai Ctr Syst Biomed, Shanghai 200240, Peoples R China; 4.Chinese Acad Sci, Inst Zool, Lab Mol Carcinogenesis & Targeted Therapy Canc, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 6.SJTUSM, Rui Jin Hosp, Shanghai Inst Hematol, Samuel Waxman Canc Res Fdn,Joint Translat Res Ctr, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhen, Tao,Wu, Chuan-Feng,Liu, Ping,et al. Targeting of AML1-ETO in t(8;21) Leukemia by Oridonin Generates a Tumor Suppressor-Like Protein[J]. SCIENCE TRANSLATIONAL MEDICINE,2012,4(127). |
| APA | Zhen, Tao.,Wu, Chuan-Feng.,Liu, Ping.,Wu, Hai-Yan.,Zhou, Guang-Biao.,...&Chen, Zhu.(2012).Targeting of AML1-ETO in t(8;21) Leukemia by Oridonin Generates a Tumor Suppressor-Like Protein.SCIENCE TRANSLATIONAL MEDICINE,4(127). |
| MLA | Zhen, Tao,et al."Targeting of AML1-ETO in t(8;21) Leukemia by Oridonin Generates a Tumor Suppressor-Like Protein".SCIENCE TRANSLATIONAL MEDICINE 4.127(2012). |
入库方式： OAI收割
来源：上海药物研究所
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