Role and Mechanism of the Interaction of BCR-ABL with E3 Ligase c-CBL in Targeting Therapy of Chronic Myelogenous Leukemia
文献类型：期刊论文
| 作者 | Mao Jianhua2; Huang Qiuhua2; Liu Ping2; Luo Cheng1 ; Xi Xiaodong2
|
| 刊名 | Journal of Experimental Hematology
 |
| 出版日期 | 2017 |
| 卷号 | 25期号:1页码:42-49 |
| 关键词 | BCR-ABL c-CBL BCR-ABL c-CBL chronic myelogenous leukemia arsenic targeting therapy |
| ISSN号 | 1009-2137 |
| 其他题名 | BCR-ABL与泛素E3连接酶c-CBL的相互作用在慢性髓系白血病靶向治疗中的作用及相关机制研究 |
| 文献子类 | Article |
| 英文摘要 | Objective: To explore the interaction domains between BCR-ABL and E3 liagase c-CBL, so as to reveal the structure-basis for the arsenic to treat chronic myelogenous leukemia(CML). Methods: The interactional interface of BCR-ABL and c-CBL was simulated and analyzed according to the available structure model. Based on the structural information, the WT and mutant Migr1-BCR-ABL-GFP (DeltaSH2,DeltaTyrKC,DeltaSH2/TyrKC (S/H)) and pFlag-c-CBL (DeltaRF) were constructed and co-transfected into the 293T and HeLa cells. The co-immunoprecipitation (Co-IP) was performed by using M2 beads (anti-Flag), anti-GFP antibody and protein A beads, and the interaction was identified by using GFP and M2 antibody, respectively. Moreover, the colocalization of BCR-ABL and c-CBL was further evaluated by using immunofluorescent (IF) assay in transfected HeLa cells. Results: Co-IP demonstrated that the TyrKC domain of BCR-ABL was primarily involved in the interaction with c-CBL, while both the SH2 domain of BCR-ABL and the RF domain of c-CBL also participated in the interaction to a certain degree, which were consistent with the structure-based simulation. IF elucidated that the colocalization of BCR-ABL and c-CBL was almost entirely vanished when the deleted TyrKC domain of BCR-ABL was co-transfected with c-CBL, which were elegantly coincident with the results from Co-IP. Conclusion: The TyrKC domain of BCR-ABL is sufficient and necessary to mediate the interaction between BCR-ABL and c-CBL, the SH2 domain of BCR-ABL and the RF domain of c-CBL are also involved in the association between the two proteins. It suggests that the association of BCR-ABL and c-CBL can modulate the stability and degradation of BCR-ABL, thus illustrating the molecular mechanisms of the targeting therapy for CML by arsenic. |
| 资助项目 | 国家重大基础研究计划项目973项目[00000000] ; 国家自然科学基金[00000000] ; 上海市浦江人才计划项目[00000000] ; 上海市自然科学基金项目[00000000] ; 上海市青年科技启明星项目[00000000] ; 教育部高等学校博士学科点专项科研基金项目(新教师类)[00000000] |
| WOS研究方向 | Oncology (provided by Clarivate Analytics) |
| 语种 | 中文 |
| CSCD记录号 | CSCD:5930946 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/269183]  |
| 专题 | 药物发现与设计中心 |
| 作者单位 | 1.State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. 2.State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.; |
| 推荐引用方式 GB/T 7714 | Mao Jianhua,Huang Qiuhua,Liu Ping,et al. Role and Mechanism of the Interaction of BCR-ABL with E3 Ligase c-CBL in Targeting Therapy of Chronic Myelogenous Leukemia[J]. Journal of Experimental Hematology,2017,25(1):42-49. |
| APA | Mao Jianhua,Huang Qiuhua,Liu Ping,Luo Cheng,&Xi Xiaodong.(2017).Role and Mechanism of the Interaction of BCR-ABL with E3 Ligase c-CBL in Targeting Therapy of Chronic Myelogenous Leukemia.Journal of Experimental Hematology,25(1),42-49. |
| MLA | Mao Jianhua,et al."Role and Mechanism of the Interaction of BCR-ABL with E3 Ligase c-CBL in Targeting Therapy of Chronic Myelogenous Leukemia".Journal of Experimental Hematology 25.1(2017):42-49. |
入库方式： OAI收割
来源：上海药物研究所
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