Reference - Detail
| RRC ID | 2280 |
|---|---|
| Author | Hayashi R, Goto Y, Ikeda R, Yokoyama KK, Yoshida K. |
| Title | CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional activation and cell proliferation. |
| Journal | J Biol Chem |
| Abstract |
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. |
| Volume | 281(47) |
| Pages | 35633-48 |
| Published | 2006-11-24 |
| DOI | 10.1074/jbc.M603800200 |
| PII | S0021-9258(20)68111-X |
| PMID | 16984923 |
| MeSH | Amino Acid Sequence Cell Cycle Cell Cycle Proteins / metabolism Cell Cycle Proteins / physiology* Cell Line, Tumor Cell Nucleus / metabolism* Cell Proliferation E2F Transcription Factors / metabolism E2F Transcription Factors / physiology* Gene Expression Regulation* HeLa Cells Humans Molecular Sequence Data Retinoblastoma Protein / metabolism Sequence Homology, Amino Acid Tissue Distribution Transcriptional Activation |
| IF | 4.238 |
| Times Cited | 36 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Wikipedia |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | FLAG-tagged p300 () HA-tagged CBP () |
| Human and Animal Cells | HeLa(RCB0007) |