title: Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2.
abstract: We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2-knockout (Jdp2KO) mice by targeting exon-1 to disrupt the site of initiation of transcription. The epidermal thickening of skin from the Jdp2KO mice after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) proceeded more rapidly than that of control mice, and more proliferating cells were found at the epidermis. Fibroblasts derived from embryos of Jdp2KO mice proliferated faster and formed more colonies than fibroblasts from wild-type mice. JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA. Furthermore, reintroduction of JDP2 resulted in the repression of transcription of ccna2 and of cell-cycle progression. Thus, transcription of the gene for cyclin-A2 appears to be a direct target of JDP2 in the suppression of cell proliferation.
authors.affiliation: RIKEN BioResource Center, Ibaraki, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: K
authors.initials: K
authors.lastname: Nakade
authors.forename: Y-C
authors.initials: YC
authors.lastname: Huang
authors.forename: Z-W
authors.initials: ZW
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Masuzaki
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: A
authors.initials: A
authors.lastname: Yoshiki
authors.forename: N
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: C-H
authors.initials: CH
authors.lastname: Lee
authors.forename: W-C
authors.initials: WC
authors.lastname: Yang
authors.forename: E-M
authors.initials: EM
authors.lastname: Tsai
authors.forename: Y
authors.initials: Y
authors.lastname: Obata
authors.forename: K K
authors.initials: KK
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D056751:Cyclin A2 / Q000235:genetics* / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D004817:Epidermis / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D055786:Gene Knockout Techniques; D017930:Genes, Reporter / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D056751:Cyclin A2; D016213:Cyclins; C491386:Jundp2 protein, mouse; D012097:Repressor Proteins; D018844:Cyclin-Dependent Kinases
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