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)