Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation
文献类型:期刊论文
作者 | Zhou, Jiangang1; Feng, Xi1; Ban, Bin1; Liu, Jingxia1; Wang, Zhou2; Xiao, Wuhan1 |
刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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出版日期 | 2009-07-10 |
卷号 | 284期号:28页码:19142-19152 |
关键词 | MIXED LINEAGE LEUKEMIA ACUTE MYELOID-LEUKEMIA MLL-ELL TUMOR-GROWTH STEM-CELLS GENE EXPRESSION ANGIOGENESIS P53 POLYMERASE |
ISSN号 | 0021-9258 |
通讯作者 | Xiao, WH, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China |
中文摘要 | 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. |
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. |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
学科主题 | Biochemistry & Molecular Biology |
类目[WOS] | Biochemistry & Molecular Biology |
研究领域[WOS] | Biochemistry & Molecular Biology |
关键词[WOS] | MIXED LINEAGE LEUKEMIA ; ACUTE MYELOID-LEUKEMIA ; MLL-ELL ; TUMOR-GROWTH ; STEM-CELLS ; GENE ; EXPRESSION ; ANGIOGENESIS ; P53 ; POLYMERASE |
收录类别 | SCI |
资助信息 | National Natural Science Foundation of China Grant (Youth Foundation) [30700440] |
语种 | 英语 |
WOS记录号 | WOS:000267711500062 |
公开日期 | 2010-10-13 |
源URL | [http://ir.ihb.ac.cn/handle/152342/7670] ![]() |
专题 | 水生生物研究所_中科院水生所知识产出(2009年前)_期刊论文 |
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 |
推荐引用方式 GB/T 7714 | Zhou, Jiangang,Feng, Xi,Ban, Bin,et al. Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2009,284(28):19142-19152. |
APA | Zhou, Jiangang,Feng, Xi,Ban, Bin,Liu, Jingxia,Wang, Zhou,&Xiao, Wuhan.(2009).Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation.JOURNAL OF BIOLOGICAL CHEMISTRY,284(28),19142-19152. |
MLA | Zhou, Jiangang,et al."Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation".JOURNAL OF BIOLOGICAL CHEMISTRY 284.28(2009):19142-19152. |
入库方式: OAI收割
来源:水生生物研究所
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