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Originally published In Press as doi:10.1074/jbc.M208288200 on December 17, 2002
J. Biol. Chem., Vol. 278, Issue 8, 6018-6026, February 21, 2003
Regulation of Lipocalin-type Prostaglandin D Synthase Gene
Expression by Hes-1 through E-box and Interleukin-1 via Two
NF- B Elements in Rat Leptomeningeal Cells*
Ko
Fujimori §,
Yasushi
Fujitani ¶,
Keiichi
Kadoyama ,
Haruko
Kumanogoh ,
Koichi
Ishikawa , and
Yoshihiro
Urade **
From the Core Research for Evolutional Science and Technology,
Japan Science and Technology Corporation and the
Department of Molecular Behavioral Biology, Osaka
Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874 and the
Institute for Molecular and Cellular Regulation, Gunma
University, Showa-machi, Maebashi, Gunma 371-8512, Japan
The promoter function of the rat lipocalin-type
prostaglandin D synthase (L-PGDS) gene was characterized in primary
cultures of leptomeningeal cells prepared from the neonatal rat brain. Luciferase reporter assays with deletion and site-directed mutation of
the promoter region ( 1250 to +77) showed that an AP-2 element at
109 was required for activation and an E-box at +57, for repression. Binding of nuclear factors to each of these cis-elements
was demonstrated by an electrophoretic mobility shift assay. Several
components of the Notch-Hes signaling pathway, Jagged,
Notch1, Notch3, and Hes-1, were
expressed in the leptomeningeal cells. Human Hes-1 co-expressed in the
leptomeningeal cells bound to the E-box of the rat L-PGDS gene, and
repressed the promoter activity of the rat L-PGDS gene in a
dose-dependent manner. The L-PGDS gene expression was
up-regulated slowly by interleukin-1 to the maximum level at 24 h. The reporter assay with deletion and mutation revealed that two
NF- B elements at 1106 and 291 were essential for this up-regulation. Binding of two NF- B subunits, p65 and c-Rel, to these
two NF- B elements occurred after the interleukin-1 treatment. Therefore, the L-PGDS gene is the first gene identified as the target
for the Notch-Hes signal through the E-box among a variety of genes
involved in the prostanoid biosynthesis, classified to the lipocalin
family, and expressed in the leptomeninges. Moreover, the L-PGDS gene
is a unique gene that is activated slowly by the NF- B system.
*
This work was supported in part by a grant from the program
for Core Research for Evolutional Science and Technology of Japan Science Technology Corporation (to Y. U.), Grant-in-aid for Scientific Research 12558078 from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to Y. U.), grants from the Ground Research Announcement for Space Utilization Promotion from the Japan
Space Forum (to Y. U.), the Pilot Applied Research Project for the
Industrial Use of Space from the National Space Development Agency of
Japan (NASDA) and Japan Space Utilization Promotion Center
(JSUP) (to Y. U.), the Takeda Science Foundation (to K. F., Y. F.,
H. K., and Y. U.), the Special Coordination Fund for Promoting
Science and Technology (to Y. U.), and Osaka City.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
Present address: Environmental Health Science Laboratory, Sumitomo
Chemical Co., Ltd., 1-98 Kasugadenaka 3-chome, Konohana-ku, Osaka
554-8558, Japan.
¶
Present address: Pharmaceutical Research Division, Takeda
Chemical Industries, Ltd., 17-85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan.
**
To whom correspondence should be addressed. Tel.: 81-6-6872-4851;
Fax: 81-6-6872-2841; E-mail: uradey@obi.or.jp.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
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