HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 284, Issue 2, 872-883, January 9, 2009

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 284/2/872    most recent M807185200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sasaki, Y. Articles by Tokino, T. Search for Related Content PubMed PubMed Citation Articles by Sasaki, Y. Articles by Tokino, T. Social Bookmarking                      What's this?

p53 Family Members Regulate the Expression of the Apolipoprotein D Gene^*

Yasushi Sasaki, Hideaki Negishi, Ryota Koyama, Naoki Anbo, Kanae Ohori, Masashi Idogawa, Hiroaki Mita, Minoru Toyota, Kohzoh Imai, Yasuhisa Shinomura, and Takashi Tokino¹

From the Department of Molecular Biology, Cancer Research Institute and First Department of Internal Medicine, Sapporo Medical University, S-1, W-17, Chuo-ku, Sapporo, 060-8556 Japan

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.

Received for publication, September 16, 2008 , and in revised form, November 10, 2008.

^* This work was supported in part by grants-in-aid for cancer research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Primary array data sets can be accessed through the NCBI Gene Expression Omnibus (GEO) under GEO accession number GSE13504 [NCBI GEO] .

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1 and 2.

¹ To whom correspondence should be addressed: Dept. of Molecular Biology, Cancer Research Institute, Sapporo Medical University, S-1, W-17, Chuo-ku, Sapporo, 060-8556 Japan. Tel.: 81-11-611-2111 (ext. 2410); Fax: 81-11-618-3313; E-mail: tokino{at}sapmed.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?