論文

査読有り 国際誌
2017年5月30日

A-kinase anchoring protein BIG3 coordinates oestrogen signalling in breast cancer cells.

Nature communications
  • Tetsuro Yoshimaru
  • Masaya Ono
  • Yoshimi Bando
  • Yi-An Chen
  • Kenji Mizuguchi
  • Hiroshi Shima
  • Masato Komatsu
  • Issei Imoto
  • Keisuke Izumi
  • Junko Honda
  • Yasuo Miyoshi
  • Mitsunori Sasa
  • Toyomasa Katagiri
  • 全て表示

8
開始ページ
15427
終了ページ
15427
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/ncomms15427
出版者・発行元
NATURE PUBLISHING GROUP

Approximately 70% of breast cancer cells express oestrogen receptor alpha (ER alpha). Previous studies have shown that the Brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex has a crucial role in these cells. However, it remains unclear how BIG3 regulates the suppressive activity of PHB2. Here we demonstrate that BIG3 functions as an A-kinase anchoring protein that binds protein kinase A (PKA) and the alpha isoform of the catalytic subunit of protein phosphatase 1 (PP1C alpha), thereby dephosphorylating and inactivating PHB2. E2-induced PKA-mediated phosphorylation of BIG3-S305 and -S1208 serves to enhance PP1C alpha activity, resulting in E2/ER alpha signalling activation via PHB2 inactivation due to PHB2-S39 dephosphorylation. Furthermore, an analysis of independent cohorts of ER alpha-positive breast cancers patients reveal that both BIG3 overexpression and PHB2-S39 dephosphorylation are strongly associated with poor prognosis. This is the first demonstration of the mechanism of E2/ER alpha signalling activation via the BIG3-PKA-PP1C alpha tri-complex in breast cancer cells.

リンク情報
DOI
https://doi.org/10.1038/ncomms15427
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28555617
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512694
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000402304300001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/ncomms15427
  • ISSN : 2041-1723
  • PubMed ID : 28555617
  • PubMed Central 記事ID : PMC5512694
  • Web of Science ID : WOS:000402304300001

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