| RNA interference against mixed lineage leukemia 5 resulted in cell cycle arrest. | |
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MedLine Citation:
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PMID: 18573682 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mixed lineage leukemia 5 (MLL5) encodes a mammalian trithorax group (TrxG) protein located within chromosome band 7q22, which is a frequently deleted region found in acute myeloid malignancies. Trithorax and polycomb (PcG) group proteins are evolutionarily conserved transcriptional regulators that maintain the expression of Homeobox (HOX) genes at the epigenetic level during development. Recently, the emerging roles of TrxG and PcG group proteins in cell cycle regulation have begun to be elucidated. In this study, we demonstrated that the mammalian trxG protein MLL5 is involved in multiple cell cycle regulation. Knockdown of MLL5 by small interfering RNA resulted in the retarded cell growth and attenuated intake of BrdU in multiple tumor and normal diploid cells. The cell cycle arrest induced by knockdown of MLL5 took place at both the G1 and G2/M phases. This growth-inhibitory effect and dual-phase arrest were also found in p53-knockout cell lines, suggesting that the transactivation activity of p53 was dispensable for the MLL5-knockdown-mediated cell cycle arrest. In addition, up-regulation of cyclin-dependent kinase inhibitor p21 and de-phosphorylation of retinoblastoma protein were observed in all cell lines tested regardless of their p53 status. Taken together, our data suggest that silencing of MLL5 leads to up-regulation of p21 and dephosphorylation of pRb, which at least partially contributes to the G1 phase and G2/M phase arrest. These findings provide evidence that MLL5 might be an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages. |
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Authors:
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Fei Cheng; Jie Liu; Shun Hui Zhou; Xiao Ning Wang; Jun Fang Chew; Lih-Wen Deng |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-05-15 |
Journal Detail:
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Title: The international journal of biochemistry & cell biology Volume: 40 ISSN: 1357-2725 ISO Abbreviation: Int. J. Biochem. Cell Biol. Publication Date: 2008 |
Date Detail:
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Created Date: 2008-08-05 Completed Date: 2008-10-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508482 Medline TA: Int J Biochem Cell Biol Country: England |
Other Details:
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Languages: eng Pagination: 2472-81 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. chenfei@nus.edu.sg |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / physiology* Cell Line Cyclin-Dependent Kinase Inhibitor p21 / genetics, metabolism DNA-Binding Proteins* / genetics, metabolism Humans RNA Interference Retinoblastoma Protein / genetics, metabolism Tumor Suppressor Protein p53 / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA-Binding Proteins; 0/MLL5 protein, human; 0/Retinoblastoma Protein; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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