| E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis. | |
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MedLine Citation:
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PMID: 19960022 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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E2F1 is a positive regulator of cell cycle progression and also a potent inducer of apoptosis, especially when activated by DNA damage. We identified E2F1-inducible microRNAs (miRNAs) by microarray hybridization and found that the levels of miRNAs 449a and 449b, as well as their host gene CDC20B, are strongly upregulated by E2F1. High miR-449 levels were found in testes, lung, and trachea, but not in testicular and other cancer cells. MiR-449a/b structurally resemble the p53-inducible miRNA 34 family. In agreement with a putative tumor-suppressive role, miR-449a as well as miR-34a reduced proliferation and strongly promoted apoptosis by at least partially p53-independent mechanisms. Both miRNAs reduced the levels of CDK6, implying miR-449 in a negative feedback mechanism for E2F1. Moreover, miR-449a and miR-34a diminished the deacetylase Sirt1 and augmented p53 acetylation. We propose that both miRNAs provide a twofold safety mechanism to avoid excessive E2F1-induced proliferation by cell cycle arrest and by apoptosis. While responding to different transactivators, miRNAs 449 and 34 each repress E2F1, but promote p53 activity, allowing efficient cross-talk between two major DNA damage-responsive gene regulators. |
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Authors:
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M Lizé; S Pilarski; M Dobbelstein |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-04 |
Journal Detail:
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Title: Cell death and differentiation Volume: 17 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-15 Completed Date: 2010-07-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 452-8 Citation Subset: IM |
Affiliation:
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Department of Molecular Oncology, Göttingen Center of Molecular Biosciences -GZMB, Ernst Caspari Haus, University of Göttingen, Justus von Liebig Weg 11, 37077 Göttingen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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physiology* Cell Line, Tumor Cell Proliferation* Cyclin-Dependent Kinase 6 / genetics, metabolism E2F1 Transcription Factor / genetics, metabolism* Gene Expression Regulation, Neoplastic Humans MicroRNAs / genetics, metabolism* Microarray Analysis Sirtuins / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/E2F1 Transcription Factor; 0/MIRN34 microRNA, human; 0/MIRN449 microRNA, human; 0/MicroRNAs; EC 2.7.11.22/Cyclin-Dependent Kinase 6; EC 3.5.1.-/Sirtuins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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