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学科主题: Biochemistry & Molecular Biology
题名: Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation
作者: Zhou, Jiangang1; Feng, Xi1; Ban, Bin1; Liu, Jingxia1; Wang, Zhou2; Xiao, Wuhan1
通讯作者: Xiao, WH, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China
关键词: MIXED LINEAGE LEUKEMIA ; ACUTE MYELOID-LEUKEMIA ; MLL-ELL ; TUMOR-GROWTH ; STEM-CELLS ; GENE ; EXPRESSION ; ANGIOGENESIS ; P53 ; POLYMERASE
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2009-07-10
DOI: 10.1074/jbc.M109.010439
卷: 284, 期:28, 页:19142-19152
收录类别: SCI
文章类型: Article
部门归属: [Zhou, Jiangang; Feng, Xi; Ban, Bin; Liu, Jingxia; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China; [Wang, Zhou] Univ Pittsburgh, Inst Canc, Dept Urol, Sch Med, Pittsburgh, PA 15232 USA
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China Grant (Youth Foundation) [30700440]
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
摘要: The eleven-nineteen lysine-rich leukemia (ELL) gene undergoes translocation and fuses in-frame to the multiple lineage leukemia gene in a substantial proportion of patients suffering from acute forms of leukemia. Studies show that ELL indirectly modulates transcription by serving as a regulator for transcriptional elongation as well as for p53, U19/Eaf2, and steroid receptor activities. Our in vitro and in vivo data demonstrate that ELL could also serve as a transcriptional factor to directly induce transcription of the thrombospondin-1 (TSP-1) gene. Experiments using ELL deletion mutants established that full-length ELL is required for the TSP-1 up-regulation and that the trans-activation domain likely resides in the carboxyl terminus. Moreover, the DNA binding domain may localize to the first 45 amino acids of ELL. Not surprisingly, multiple lineage leukemia-ELL, which lacks these amino acids, did not induce expression from the TSP-1 promoter. In addition, the ELL core-response element appears to localize in the -1426 to -1418 region of the TSP-1 promoter. Finally, studies using zebrafish confirmed that ELL regulates TSP-1 mRNA expression in vivo, and ELL could inhibit zebrafish vasculogenesis, at least in part, through up-regulating TSP-1. Given the importance of TSP-1 as an anti-angiogenic protein, our findings may have important ramifications for better understanding cancer.
英文摘要: The eleven-nineteen lysine-rich leukemia (ELL) gene undergoes translocation and fuses in-frame to the multiple lineage leukemia gene in a substantial proportion of patients suffering from acute forms of leukemia. Studies show that ELL indirectly modulates transcription by serving as a regulator for transcriptional elongation as well as for p53, U19/Eaf2, and steroid receptor activities. Our in vitro and in vivo data demonstrate that ELL could also serve as a transcriptional factor to directly induce transcription of the thrombospondin-1 (TSP-1) gene. Experiments using ELL deletion mutants established that full-length ELL is required for the TSP-1 up-regulation and that the trans-activation domain likely resides in the carboxyl terminus. Moreover, the DNA binding domain may localize to the first 45 amino acids of ELL. Not surprisingly, multiple lineage leukemia-ELL, which lacks these amino acids, did not induce expression from the TSP-1 promoter. In addition, the ELL core-response element appears to localize in the -1426 to -1418 region of the TSP-1 promoter. Finally, studies using zebrafish confirmed that ELL regulates TSP-1 mRNA expression in vivo, and ELL could inhibit zebrafish vasculogenesis, at least in part, through up-regulating TSP-1. Given the importance of TSP-1 as an anti-angiogenic protein, our findings may have important ramifications for better understanding cancer.
关键词[WOS]: MIXED LINEAGE LEUKEMIA ; ACUTE MYELOID-LEUKEMIA ; MLL-ELL ; TUMOR-GROWTH ; STEM-CELLS ; GENE ; EXPRESSION ; ANGIOGENESIS ; P53 ; POLYMERASE
语种: 英语
WOS记录号: WOS:000267711500062
ISSN号: 0021-9258
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/152342/7670
Appears in Collections:中科院水生所知识产出(2009年前)_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China
2.Univ Pittsburgh, Inst Canc, Dept Urol, Sch Med, Pittsburgh, PA 15232 USA

Recommended Citation:
Zhou, Jiangang; Feng, Xi; Ban, Bin; Liu, Jingxia; Wang, Zhou; Xiao, Wuhan.Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation,JOURNAL OF BIOLOGICAL CHEMISTRY,2009,284(28):19142-19152
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