| Direct control of cell cycle gene expression by proto-oncogene product ACTR, and its autoregulation underlies its transforming activity. | |
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MedLine Citation:
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PMID: 16648476 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ACTR (also called AIB1 and SRC-3) was identified as a coactivator for nuclear receptors and is linked to multiple types of human cancer due to its frequent overexpression. However, the molecular mechanism of ACTR oncogenicity and its function independent of nuclear receptors remain to be defined. We demonstrate here that ACTR is required for both normal and malignant human cells to effectively enter S phase. RNA interference-mediated depletion and chromatin immunoprecipitation assays show that endogenous ACTR directly controls the expression of genes important for initiation of DNA replication, which include cdc6, cdc25A, MCM7, cyclin E, and Cdk2. Moreover, consistent with its critical role in cell cycle control, ACTR expression appears to be cell cycle regulated, which involves E2F. Interestingly, ACTR is recruited to its own promoter at the G1/S transition and activates its own expression, suggesting a positive feedback mechanism for ACTR action in the control of cell cycle progression and for its aberrant expression in cancers. Importantly, overexpression of ACTR alone transforms human mammary epithelial cells, which requires its association with E2F. These findings reveal a novel role for ACTR in cell cycle control and support the notion that the ability of aberrant ACTR to deregulate the cell cycle through E2F underlies its oncogenicity in human cancers. |
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Authors:
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Maggie C Louie; Alexey S Revenko; June X Zou; Jennifer Yao; Hong-Wu Chen |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular and cellular biology Volume: 26 ISSN: 0270-7306 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-05-01 Completed Date: 2006-06-09 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 3810-23 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Medicine, UCD Cancer Center/Basic Science, University of California at Davis, Sacramento, California 95817, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetyltransferases
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genetics,
metabolism* Adenoviridae / genetics Blotting, Western Breast Neoplasms / genetics, pathology Cell Cycle* Cell Cycle Proteins / antagonists & inhibitors Cell Line Cell Line, Tumor Cell Proliferation Chromatin Immunoprecipitation Diploidy Female Fibroblasts / metabolism Fluorescein-5-isothiocyanate Fluorescent Dyes Gene Expression Regulation* Gene Expression Regulation, Neoplastic* Genes, Reporter Genes, cdc* Glioblastoma / genetics, pathology Green Fluorescent Proteins / metabolism Hela Cells Histone Acetyltransferases Humans Indoles Luciferases / metabolism Microscopy, Fluorescence Nuclear Receptor Coactivator 3 Oncogene Proteins / genetics, metabolism* Promoter Regions, Genetic RNA, Small Interfering / metabolism Reverse Transcriptase Polymerase Chain Reaction Trans-Activators / genetics, metabolism* Tumor Stem Cell Assay |
| Grant Support | |
ID/Acronym/Agency:
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DK60019/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Fluorescent Dyes; 0/Indoles; 0/Oncogene Proteins; 0/RNA, Small Interfering; 0/Trans-Activators; 147336-22-9/Green Fluorescent Proteins; 3326-32-7/Fluorescein-5-isothiocyanate; 47165-04-8/DAPI; EC 1.13.12.-/Luciferases; EC 2.3.1.-/Acetyltransferases; EC 2.3.1.48/Histone Acetyltransferases; EC 2.3.1.48/NCOA3 protein, human; EC 2.3.1.48/Nuclear Receptor Coactivator 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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