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Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation
Zhou, Jiangang1; Feng, Xi1; Ban, Bin1; Liu, Jingxia1; Wang, Zhou2; Xiao, Wuhan1; Xiao, WH, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China
2009-07-10
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume284Issue:28Pages:19142-19152
AbstractThe 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.; 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.
SubtypeArticle
KeywordMixed Lineage Leukemia Acute Myeloid-leukemia Mll-ell Tumor-growth Stem-cells Gene Expression Angiogenesis P53 Polymerase
Department[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
Subject AreaBiochemistry & Molecular Biology
DOI10.1074/jbc.M109.010439
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Natural Science Foundation of China Grant (Youth Foundation) [30700440] ; National Natural Science Foundation of China Grant (Youth Foundation) [30700440] ; National Natural Science Foundation of China Grant (Youth Foundation) [30700440] ; National Natural Science Foundation of China Grant (Youth Foundation) [30700440]
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000267711500062
WOS KeywordMIXED LINEAGE LEUKEMIA ; ACUTE MYELOID-LEUKEMIA ; MLL-ELL ; TUMOR-GROWTH ; STEM-CELLS ; GENE ; EXPRESSION ; ANGIOGENESIS ; P53 ; POLYMERASE
Funding OrganizationNational Natural Science Foundation of China Grant (Youth Foundation) [30700440] ; National Natural Science Foundation of China Grant (Youth Foundation) [30700440] ; National Natural Science Foundation of China Grant (Youth Foundation) [30700440] ; National Natural Science Foundation of China Grant (Youth Foundation) [30700440]
Citation statistics
Cited Times:21[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/152342/7670
Collection期刊论文
Corresponding AuthorXiao, WH, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China
Affiliation1.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
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, WH, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China.(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.
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