| RRC ID |
2280
|
| 著者 |
Hayashi R, Goto Y, Ikeda R, Yokoyama KK, Yoshida K.
|
| タイトル |
CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional activation and cell proliferation.
|
| ジャーナル |
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.
|
| 巻・号 |
281(47)
|
| ページ |
35633-48
|
| 公開日 |
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
|
| 引用数 |
36
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
FLAG-tagged p300 ()
HA-tagged CBP () |
| ヒト・動物細胞 |
HeLa(RCB0007) |
