論文

査読有り
2017年8月

Mediator 1 contributes to enamel mineralization as a coactivator for Notch1 signaling and stimulates transcription of the alkaline phosphatase gene

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Keigo Yoshizaki
  • Lizhi Hu
  • Thai Nguyen
  • Kiyoshi Sakai
  • Masaki Ishikawa
  • Ichiro Takahashi
  • Satoshi Fukumoto
  • Pamela K. DenBesten
  • Daniel D. Bikle
  • Yuko Oda
  • Yoshihiko Yamada
  • 全て表示

292
33
開始ページ
13531
終了ページ
13540
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M117.780866
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Tooth enamel is mineralized through the differentiation of multiple dental epithelia including ameloblasts and the stratum intermedium (SI), and this differentiation is controlled by several signaling pathways. Previously, we demonstrated that the transcriptional coactivator Mediator 1 (MED1) plays a critical role in enamel formation. For instance, conditional ablation of Med1 in dental epithelia causes functional changes in incisor-specific dental epithelial stem cells, resulting in mineralization defects in the adult incisors. However, the molecular mechanism by which Med1 deficiency causes these abnormalities is not clear. Here, we demonstrated that Med1 ablation causes early SI differentiation defects resulting in enamel hypoplasia of the Med1-deficient molars. Med1 deletion prevented Notch1-mediated differentiation of the SI cells resulting in decreased alkaline phosphatase (ALPL), which is essential for mineralization. However, it does not affect the ability of ameloblasts to produce enamel matrix proteins. Using the dental epithelial SF2 cell line, we demonstrated that MED1 directly activates transcription of the Alpl gene through the stimulation of Notch1 signaling by forming a complex with cleaved Notch1-RBP-Jk on the Alpl promoter. These results suggest that MED1 may be essential for enamel matrix mineralization by serving as a coactivator for Notch1 signaling regulating transcription of the Alpl gene.

リンク情報
DOI
https://doi.org/10.1074/jbc.M117.780866
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28673966
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000407942400034&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M117.780866
  • ISSN : 0021-9258
  • eISSN : 1083-351X
  • PubMed ID : 28673966
  • Web of Science ID : WOS:000407942400034

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