2017年5月30日
A-kinase anchoring protein BIG3 coordinates oestrogen signalling in breast cancer cells.
Nature communications
- 巻
- 8
- 号
- 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