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

• Yoshimaru, Tetsuro

• Ono, Masaya

• Bando, Yoshimi

• Chen, Yi-An

• Mizuguchi, Kenji

• Shima, Hiroshi

• Komatsu, Masato

• Imoto, Issei

• Izumi, Keisuke

• Honda, Junko

• Miyoshi, Yasuo

• Sasa, Mitsunori

• Katagiri, Toyomasa

Abstract

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.

Journal

• Nature Communications

  Nature Communications 8 15427-, 2017-05-30

  Springer Nature

Keywords

• General Physics and Astronomy
• General Biochemistry, Genetics and Molecular Biology
• General Chemistry
• Multidisciplinary

Details

• CRID: 1050564287756278912
• NII Article ID: 120006535065
• NII Book ID: AA12645905
• ISSN: 20411723
• DOI: 10.1038/ncomms15427
• Web Site: http://repo.lib.tokushima-u.ac.jp/112449
• Web Site: https://www.nature.com/articles/ncomms15427.pdf
• Web Site: https://www.nature.com/articles/ncomms15427
• Web Site: http://www.nature.com/doifinder/10.1038/ncomms15427
• Text Lang: en
• Article Type: journal article
• Data Source:
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  • Crossref
  • CiNii Articles
  • KAKEN