title: p53 family members regulate the expression of the apolipoprotein D gene.
abstract: p73 and p63 are members of the p53 gene family that play an important role in development and homeostasis, mainly by regulating transcription of a variety of genes. We report here that apolipoprotein D (apoD), a member of the lipocalin superfamily of lipid transport proteins, is a direct transcriptional target of the p53 family member genes. We found that the expression of apoD was specifically up-regulated by either TAp73 or TAp63 but not significantly by p53. In addition, apoD transcription is activated in response to cisplatin in a manner dependent on endogenous p73. By using small interference RNA designed to target p73, we demonstrated that silencing endogenous p73 abolishes induction of apoD transcription following cisplatin treatment. We also identified a p73/p63-binding site in the promoter of the apoD gene that is responsive to the p53 family members. The ectopic expression of TAp73 as well as the addition of recombinant human apoD to culture medium induced the osteoblastic differentiation of the human osteosarcoma cell line Saos-2, as assessed by alkaline phosphatase activity. Importantly, apoD knockdown abrogated p73-mediated alkaline phosphatase induction. Moreover, TAp73-mediated apoD expression was able to induce morphological differentiation, as well as expression of neuronal markers, in the human neuroblastoma cell line SH-SY5Y. These results suggest that apoD induction may mediate the activity of p73 in normal development.
authors.affiliation: Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, S-1, W-17, Chuo-ku, Sapporo, 060-8556 Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Negishi
authors.forename: Ryota
authors.initials: R
authors.lastname: Koyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Anbo
authors.forename: Kanae
authors.initials: K
authors.lastname: Ohori
authors.forename: Masashi
authors.initials: M
authors.lastname: Idogawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mita
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
mesh_terms: D000818:Animals; D053399:Apolipoproteins D / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D053399:Apolipoproteins D; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C477072:tp73 protein, zebrafish