JPO1/CDCA7, a novel transcription factor E2F1-induced protein, possesses intrinsic transcriptional regulator activity.
JPO1/CDCA7 was originally identified as a c-Myc-responsive gene that participates in neoplastic transformation. Here, we report the identification of JPO1/CDCA7 as a direct transcriptional target of transcription factor E2F1. We demonstrated that overexpression of E2F1 by adenoviral-mediated gene transfer upregulated JPO1/CDCA7 mRNA expression in human cells. Analysis of human and mouse JPO1/CDCA7 promoter constructs showed that an E2F-responsive sequence was necessary for E2F1-induced activation of the JPO1/CDCA7 gene transcription. Among the members of the E2F family, E2F1 to E2F4, but not E2F5 or E2F6, activated the JPO1/CDCA7 reporter construct. Chromatin immunoprecipitation analysis demonstrated that E2F1, E2F2, and E2F4 specifically bound to an E2F-responsive sequence of the human JPO1/CDCA7 gene. Like JPO2/R1, which has a homologous transcriptional regulator domain, the C-terminal cysteine-rich region of JPO1/CDCA7 protein induced transcriptional activity in a mammalian one-hybrid assay. Taken together, our results suggest that JPO1/CDCA7 is a unique transcription regulator whose expression is activated by E2F1 as well as c-Myc.
Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan.
Yuya
Y
Goto
Reiko
R
Hayashi
Tomoki
T
Muramatsu
Hitomi
H
Ogawa
Ikumi
I
Eguchi
Yasuhiro
Y
Oshida
Kiyoshi
K
Ohtani
Kenichi
K
Yoshida
D000818:Animals; D001665:Binding Sites; D050687:E2F1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D050703:E2F2 Transcription Factor / Q000378:metabolism; D050704:E2F4 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors; D014161:Transduction, Genetic
C445325:CDCA7 protein, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors