論文

査読有り
2006年10月

Transcription factor activating enhancer-binding protein-2 beta - A negative regulator of adiponectin gene expression

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Kazuhiro Ikeda
  • ,
  • Hiroshi Maegawa
  • ,
  • Satoshi Ugi
  • ,
  • Yukari Tao
  • ,
  • Yoshihiko Nishio
  • ,
  • Shuichi Tsukada
  • ,
  • Shiro Maeda
  • ,
  • Atsunori Kashiwagi

281
42
開始ページ
31245
終了ページ
31253
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M605132200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

We previously reported the association between the activating enhancer-binding protein-2 beta (AP-2 beta) transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with the disease-susceptible allele of AP-2 beta showed stronger expression in adipose tissue than those without the susceptible allele. Furthermore, overexpression of AP-2 beta leads to lipid accumulation by enhancing glucose transport and inducing insulin resistance in 3T3-L1 adipocytes. In this study we demonstrated that overexpression of AP-2 beta in 3T3-L1 adipocytes decreased the expression and secretion of adiponectin and increased those of interleukin-6 (IL-6). Interestingly, the effects of AP-2 beta on the expressions of adiponectin and IL-6 and the mechanisms by which AP-2 beta modulated their expressions were different. We found that the promoter activity of adiponectin gene was inhibited by AP-2 beta overexpression and enhanced by knockdown of endogenous AP-2 beta, whereas IL-6 was unaffected. Electrophoretic mobility shift assays revealed the existence of putative responsive elements for AP-2 beta and NF-YA in human and mouse adiponectin promoter regions, and mutation of this AP-2 beta binding site abolished the inhibitory effect of AP-2 beta. Furthermore, chromatin immunoprecipitation assays demonstrated that AP-2 beta and NF-YA competitively bind to the same region of the adiponectin promoter. Our results clearly demonstrated that AP-2 beta directly inhibits adiponectin gene expression by displacing NF-YA and binding to its promoter. We conclude that AP-2 beta might modulate the expression of adiponectin by directly inhibiting its transcriptional activity.

Web of Science ® 被引用回数 : 30

リンク情報
DOI
https://doi.org/10.1074/jbc.M605132200
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/16954217
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000241235300009&DestApp=WOS_CPL

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