Source:http://linkedlifedata.com/resource/pubmed/id/16984923
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
47
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| pubmed:dateCreated |
2006-11-20
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| pubmed:abstractText |
The TRIP-Br1/p34(SEI-1) family proteins participate in cell cycle progression by coactivating E2F1- or p53-dependent transcriptional activation. Here, we report the identification of human CDCA4 (also know as SEI-3/Hepp) as a novel target gene of transcription factor E2F and as a repressor of E2F-dependent transcriptional activation. Analysis of CDCA4 promoter constructs showed that an E2F-responsive sequence in the vicinity of the transcription initiation site is necessary for the E2F1-4-induced activation of CDCA4 gene transcription. Chromatin immunoprecipitation analysis demonstrated that E2F1 and E2F4 bound to an E2F-responsive sequence of the human CDCA4 gene. Like TRIP-Br1/p34(SEI-1) and TRIP-Br2 (SEI-2), the transactivation domain of CDCA4 was mapped within C-terminal acidic region 175-241. The transactivation function of the CDCA4 protein was inhibited by E2F1-4 and DP2, but not by E2F5-8. Inhibition of CDCA4 transactivation activity by E2F1 partially interfered with retinoblastoma protein overexpression. Conversely, CDCA4 suppressed E2F1-3-induced reporter activity. CDCA4 (but not acidic region-deleted CDCA4) suppressed E2F1-regulated gene promoter activity. These findings suggest that the CDCA4 protein functions as a suppressor at the E2F-responsive promoter. Small interfering RNA-mediated knockdown of CDCA4 expression in cancer cells resulted in up-regulation of cell growth rates and DNA synthesis. The CDCA4 protein was detected in several human cells and was induced as cells entered the G1/S phase of the cell cycle. Taken together, our results suggest that CDCA4 participates in the regulation of cell proliferation, mainly through the E2F/retinoblastoma protein pathway.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
24
|
| pubmed:volume |
281
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
35633-48
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:16984923-Amino Acid Sequence,
pubmed-meshheading:16984923-Cell Cycle,
pubmed-meshheading:16984923-Cell Cycle Proteins,
pubmed-meshheading:16984923-Cell Line, Tumor,
pubmed-meshheading:16984923-Cell Nucleus,
pubmed-meshheading:16984923-Cell Proliferation,
pubmed-meshheading:16984923-E2F Transcription Factors,
pubmed-meshheading:16984923-Gene Expression Regulation,
pubmed-meshheading:16984923-HeLa Cells,
pubmed-meshheading:16984923-Humans,
pubmed-meshheading:16984923-Molecular Sequence Data,
pubmed-meshheading:16984923-Retinoblastoma Protein,
pubmed-meshheading:16984923-Sequence Homology, Amino Acid,
pubmed-meshheading:16984923-Tissue Distribution,
pubmed-meshheading:16984923-Transcriptional Activation
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional activation and cell proliferation.
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| pubmed:affiliation |
Laboratory of Molecular and Cellular Biology, Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Kawasaki, Kanagawa 214-8571, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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