PMID:16984923
| Citation |
Hayashi, R, Goto, Y, Ikeda, R, Yokoyama, KK and Yoshida, K (2006) CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional activation and cell proliferation. J. Biol. Chem. 281:35633-48 |
|---|---|
| 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. |
| Links |
PubMed Online version:10.1074/jbc.M603800200 |
| Keywords |
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 |
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