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Progesterone-dependent induction of phospholipase C-related catalytically inactive protein 1 (PRIP-1) in decidualizing human endometrial stromal cells
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Muter, Joanne, Brighton, Paul, Lucas, Emma S., Lacey, Lauren, Shmygol, Anatoly, Quenby, Siobhan, Blanks, Andrew M. and Brosens, Jan J. (2016) Progesterone-dependent induction of phospholipase C-related catalytically inactive protein 1 (PRIP-1) in decidualizing human endometrial stromal cells. Endocrinology, 157 (7). pp. 2883-2893. doi:10.1210/en.2015-1914
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WRAP-progesterone-dependent-phospholipase-protein-human-endometrial-cells-Brosens-2016.pdf - Accepted Version - Requires a PDF viewer. Download (14Mb) | Preview |
Official URL: http://dx.doi.org/10.1210/en.2015-1914
Abstract
Decidualization denotes the transformation of endometrial stromal cells into specialized decidual cells. In pregnancy, decidual cells form a protective matrix around the implanting embryo, enabling coordinated trophoblast invasion and formation of a functional placenta. Continuous progesterone (P4) signaling renders decidual cells resistant to various environmental stressors, whereas withdrawal inevitably triggers tissue breakdown and menstruation or miscarriage. Here, we show that PLCL1, coding phospholipase C (PLC)-related catalytically inactive protein 1 (PRIP-1), is highly induced in response to P4 signaling in decidualizing human endometrial stromal cells (HESCs). Knockdown experiments in undifferentiated HESCs revealed that PRIP-1 maintains basal phosphoinositide 3-kinase/Protein kinase B activity, which in turn prevents illicit nuclear translocation of the transcription factor forkhead box protein O1 and induction of the apoptotic activator BIM. By contrast, loss of this scaffold protein did not compromise survival of decidual cells. PRIP-1 knockdown did also not interfere with the responsiveness of HESCs to deciduogenic cues, although the overall expression of differentiation markers, such as PRL, IGFBP1, and WNT4, was blunted. Finally, we show that PRIP-1 in decidual cells uncouples PLC activation from intracellular Ca2+ release by attenuating inositol 1,4,5-trisphosphate signaling. In summary, PRIP-1 is a multifaceted P4-inducible scaffold protein that gates the activity of major signal transduction pathways in the endometrium. It prevents apoptosis of proliferating stromal cells and contributes to the relative autonomy of decidual cells by silencing PLC signaling downstream of Gq protein-coupled receptors.
| Item Type: | Journal Article | ||||||
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | Endocrinology | ||||||
| Publisher: | Endocrine Society | ||||||
| ISSN: | 0013-7227 | ||||||
| Official Date: | 1 July 2016 | ||||||
| Dates: |
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| Date of first compliant deposit: | 7 November 2019 | ||||||
| Volume: | 157 | ||||||
| Number: | 7 | ||||||
| Page Range: | pp. 2883-2893 | ||||||
| DOI: | 10.1210/en.2015-1914 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Publisher Statement: | This is a pre-copyedited, author-produced version of an article accepted for publication in Endocrinology following peer review. The version of record Joanne Muter, Paul J. Brighton, Emma S. Lucas, Lauren Lacey, Anatoly Shmygol, Siobhan Quenby, Andrew M. Blanks, Jan J. Brosens, Progesterone-Dependent Induction of Phospholipase C-Related Catalytically Inactive Protein 1 (PRIP-1) in Decidualizing Human Endometrial Stromal Cells, Endocrinology, Volume 157, Issue 7, 1 July 2016, Pages 2883–2893, is available online at: http://dx.doi.org/10.1210/en.2015-1914 | ||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||
| Description: | free access |
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| Open Access Version: |
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