ID 112449
著者
Ono, Masaya National Cancer Center Research Institute
Chen, Yi-An National Institutes of Biomedical Innovation, Health and Nutrition
Mizuguchi, Kenji National Institutes of Biomedical Innovation, Health and Nutrition
Shima, Hiroshi Miyagi Cancer Center Research Institute
Komatsu, Masato Tokushima University
Honda, Junko Higashitokushima Medical Center
Miyoshi, Yasuo Hyogo College of Medicine
Sasa, Mitsunori Tokushima Breast Care Clinic
資料タイプ
学術雑誌論文
抄録
Approximately 70% of breast cancer cells express oestrogen receptor alpha (ERα). 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 α isoform of the catalytic subunit of protein phosphatase 1 (PP1Cα), thereby dephosphorylating and inactivating PHB2. E2-induced PKA-mediated phosphorylation of BIG3-S305 and -S1208 serves to enhance PP1Cα activity, resulting in E2/ERα signalling activation via PHB2 inactivation due to PHB2-S39 dephosphorylation. Furthermore, an analysis of independent cohorts of ERα-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/ERα signalling activation via the BIG3–PKA–PP1Cα tri-complex in breast cancer cells.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
8
開始ページ
15427
発行日
2017-05-30
備考
Supplementary Information : ncomms_8_15427_s1.pdf
Peer Review File : ncomms_8_15427_s2.pdf
権利情報
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所
病院
医学系