Post-translational modifications of the progesterone receptors

•Progesterone receptors (PR) are subject to posttranslational modifications (PTM).•PTMs include phosphorylation, ubiquitination, acetylation and SUMOylation.•These modifications control the classical transcriptional activity of PR.•PR PTM could be therapeutically targeted as part of breast cancer tr...

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Bibliographic Details
Published in:The Journal of steroid biochemistry and molecular biology 2014-03, Vol.140, p.80-89
Main Authors: Abdel-Hafiz, Hany A., Horwitz, Kathryn B.
Format: Article
Language:English
Subjects:
Acetylation
Animals
Breast cancer
Breast Neoplasms - metabolism
Female
Humans
Mice
Phosphorylation
Post-translational modification
Progesterone receptor
Protein Processing, Post-Translational
Receptors, Progesterone - metabolism
SUMOylation
Transcriptional activity
Ubiquitination
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Summary:•Progesterone receptors (PR) are subject to posttranslational modifications (PTM).•PTMs include phosphorylation, ubiquitination, acetylation and SUMOylation.•These modifications control the classical transcriptional activity of PR.•PR PTM could be therapeutically targeted as part of breast cancer treatment. Progesterone plays a key role in the development, differentiation and maintenance of female reproductive tissues and has multiple non-reproductive neural functions. Depending on the cell and tissue, the hormonal environment, growth conditions and the developmental stage, progesterone can either stimulate cell growth or inhibit it while promoting differentiation. Progesterone receptors (PRs) belong to the steroid hormone receptor superfamily of ligand-dependent transcription factors. PR proteins are subject to extensive post-translational modifications that include phosphorylation, acetylation, ubiquitination and SUMOylation. The interplay among these modifications is complex with alteration of the receptors by one factor influencing the impact of another. Control over these modifications is species-, tissue- and cell-specific. They in turn regulate multiple functions including PR stability, their subcellular localization, protein-protein interactions and transcriptional activity. These complexities may explain how tissue- and gene-specific differences in regulation are achieved in the same organism, by the same receptor protein and hormone. Here we review current knowledge of PR post-translational modifications and discuss how these may influence receptor function focusing on human breast cancer cells. There is much left to be learned. However, our understanding of this may help to identify therapeutic agents that target PR activity in tissue-specific, even gene-specific ways.
ISSN:0960-0760
1879-1220
DOI:10.1016/j.jsbmb.2013.12.008