ELL Inhibits E2F1 Transcriptional Activity by Enhancing E2F1 Deacetylation via Recruitment of Histone Deacetylase 1 | |
Zhang, Wei; Ji, Wei; Liu, Xing; Ouyang, Gang; Xiao, Wuhan; Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China. | |
2014-02-01 | |
Source Publication | MOLECULAR AND CELLULAR BIOLOGY
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ISSN | 0270-7306 |
Volume | 34Issue:4Pages:765-775 |
Abstract | ELL (eleven-nineteen lysine-rich leukemia protein) was first identified as a translocation partner of MLL in acute myeloid leukemia; however, the exact mechanism of its action has remained elusive. In this study, we identified ELL as a direct downstream target gene of E2F1. Coimmunoprecipitation assays showed that ELL interacted with E2F1 in vitro and in vivo, leading to inhibition of E2F1 transcriptional activity. In addition, ELL enhanced E2F1 deacetylation via recruitment of histone deacetylase 1 (HDAC1). Notably, the MLL-ELL fusion protein lost the inhibitory role of ELL in E2F1 transcriptional activity. Furthermore, DNA damage induced ELL in an E2F1-dependent manner and ELL protected cells against E2F1-dependent apoptosis. Our findings not only connect ELL to E2F1 function and uncover a novel role of ELL in response to DNA damage but also provide an insight into the mechanism for MLL-ELL-associated leukemogenesis.; ELL (eleven-nineteen lysine-rich leukemia protein) was first identified as a translocation partner of MLL in acute myeloid leukemia; however, the exact mechanism of its action has remained elusive. In this study, we identified ELL as a direct downstream target gene of E2F1. Coimmunoprecipitation assays showed that ELL interacted with E2F1 in vitro and in vivo, leading to inhibition of E2F1 transcriptional activity. In addition, ELL enhanced E2F1 deacetylation via recruitment of histone deacetylase 1 (HDAC1). Notably, the MLL-ELL fusion protein lost the inhibitory role of ELL in E2F1 transcriptional activity. Furthermore, DNA damage induced ELL in an E2F1-dependent manner and ELL protected cells against E2F1-dependent apoptosis. Our findings not only connect ELL to E2F1 function and uncover a novel role of ELL in response to DNA damage but also provide an insight into the mechanism for MLL-ELL-associated leukemogenesis. |
Subtype | Article |
Keyword | Rna-polymerase-ii Elongation-factor Ell Mixed-lineage Leukemia Dna-damage Complex Sec Cell-death Mll-ell Protein Gene Transactivation |
Department | [Zhang, Wei; Ji, Wei; Liu, Xing; Ouyang, Gang; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China |
DOI | 10.1128/MCB.00878-13 |
WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
Funding Organization | 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] ; 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] ; 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] ; 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] |
Indexed By | SCI |
Language | 英语 |
WOS Research Area | Biochemistry & Molecular Biology ; Cell Biology |
WOS Subject | Biochemistry & Molecular Biology ; Cell Biology |
WOS ID | WOS:000330583000016 |
WOS Keyword | RNA-POLYMERASE-II ; ELONGATION-FACTOR ELL ; MIXED-LINEAGE LEUKEMIA ; DNA-DAMAGE ; COMPLEX SEC ; CELL-DEATH ; MLL-ELL ; PROTEIN ; GENE ; TRANSACTIVATION |
Funding Organization | 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] ; 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] ; 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] ; 973 grant [2010CB126306]; CAS Major Scientific and Technological Project [XDA08010208]; NSFC [31071212, 91019008] |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ihb.ac.cn/handle/342005/20097 |
Collection | 水生生物分子与细胞生物学研究中心_期刊论文 |
Corresponding Author | Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China. |
Affiliation | Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China |
Recommended Citation GB/T 7714 | Zhang, Wei,Ji, Wei,Liu, Xing,et al. ELL Inhibits E2F1 Transcriptional Activity by Enhancing E2F1 Deacetylation via Recruitment of Histone Deacetylase 1[J]. MOLECULAR AND CELLULAR BIOLOGY,2014,34(4):765-775. |
APA | Zhang, Wei,Ji, Wei,Liu, Xing,Ouyang, Gang,Xiao, Wuhan,&Xiao, WH .(2014).ELL Inhibits E2F1 Transcriptional Activity by Enhancing E2F1 Deacetylation via Recruitment of Histone Deacetylase 1.MOLECULAR AND CELLULAR BIOLOGY,34(4),765-775. |
MLA | Zhang, Wei,et al."ELL Inhibits E2F1 Transcriptional Activity by Enhancing E2F1 Deacetylation via Recruitment of Histone Deacetylase 1".MOLECULAR AND CELLULAR BIOLOGY 34.4(2014):765-775. |
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