RRC ID |
1444
|
著者 |
Wei P, Taniguchi S, Sakai Y, Imamura M, Inoguchi T, Nawata H, Oda S, Nakabeppu Y, Nishimura J, Ikuyama S.
|
タイトル |
Expression of adipose differentiation-related protein (ADRP) is conjointly regulated by PU.1 and AP-1 in macrophages.
|
ジャーナル |
J Biochem
|
Abstract |
ADRP is associated with intracellular lipid droplets. We demonstrate the regulatory mechanism for ADRP expression in RAW264.7 macrophages. The ADRP mRNA expression was stimulated by PMA, and synergistically enhanced in association with its protein level in the presence of lipids. A proteasome inhibitor protected the protein from degradation under the lipid-free conditions. One of the possible sites of the PMA action was proved to be an Ets/AP-1 element in the promoter, since mutations of this site reduced the PMA-induced promoter activity, and ligation of this element led to a significant increase in the PMA-responsiveness of homologous or heterologous promoters. Mutations of this site diminished the synergistic effect on the promoter activity induced by PMA and oleic acid, suggesting a possible interaction between this site and the downstream PPARdelta site. EMSA revealed that PU.1 and AP-1 conjointly bound to this site. The juxtaposition of the two sequences was requisite for full activity, since spacer sequences between them decreased the PMA-induced activity. PI3 kinase inhibitor was found to reduce the PMA-induced mRNA expression and promoter activity in parallel with PU.1/AP-1 complex formation on EMSA. From these results, we concluded that the Ets/AP-1 site is an important cis-acting element that regulates the ADRP gene expression in macrophages.
|
巻・号 |
138(4)
|
ページ |
399-412
|
公開日 |
2005-10-1
|
DOI |
10.1093/jb/mvi136
|
PII |
138/4/399
|
PMID |
16272134
|
MeSH |
Adipose Tissue
Animals
Cells, Cultured
Gene Expression / drug effects
Gene Expression Regulation*
Macrophages / metabolism*
Membrane Proteins / biosynthesis*
Membrane Proteins / genetics
Mice
Molecular Sequence Data
PPAR delta
Perilipin-2
Promoter Regions, Genetic
Proto-Oncogene Proteins / metabolism*
RNA, Messenger / biosynthesis
Sp1 Transcription Factor / genetics*
Tetradecanoylphorbol Acetate / analogs & derivatives
Tetradecanoylphorbol Acetate / pharmacology
Trans-Activators / metabolism*
Transcription Factor AP-1 / metabolism*
|
IF |
2.476
|
引用数 |
26
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |