Expression of adipose differentiation-related protein (ADRP) is conjointly regulated by PU.1 and AP-1 in macrophages

Ping Wei, Susumu Taniguchi, Yoshiyuki Sakai, Minako Imamura, Toyoshi Inoguchi, Hajime Nawata, Shinya Oda, Yusaku Nakabeppu, Junji Nishimura, Shoichiro Ikuyama

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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. Aproteasome 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 PPARδ 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.

元の言語英語
ページ(範囲)399-412
ページ数14
ジャーナルJournal of biochemistry
138
発行部数4
DOI
出版物ステータス出版済み - 10 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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    Wei, P., Taniguchi, S., Sakai, Y., Imamura, M., Inoguchi, T., Nawata, H., Oda, S., Nakabeppu, Y., Nishimura, J., & Ikuyama, S. (2005). Expression of adipose differentiation-related protein (ADRP) is conjointly regulated by PU.1 and AP-1 in macrophages. Journal of biochemistry, 138(4), 399-412. https://doi.org/10.1093/jb/mvi136