ArticleBMC molecular biology2012
Control of progesterone receptor transcriptional synergy by SUMOylation and deSUMOylation.
Article in BMC molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Advances in the molecular mechanisms underlying progestin resistance in endometrial cancer.Fundamental research · 2025Review
- Thymoquinone Nanoparticle Induces Apoptosis and Cell Migration Retardation through Modulating of SUMOylation Process Genes in Breast Cancer Cell Line.Iranian journal of biotechnology · 2024Article
- Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma.Cancers · 2022Review
- Review
- In silico assessment of new progesterone receptor inhibitors using molecular dynamics: a new insight into breast cancer treatment.Journal of molecular modeling · 2018Article
- SUMOylation Regulates Transcription by the Progesterone Receptor A Isoform in a Target Gene Selective Manner.Diseases (Basel, Switzerland) · 2018Article
- The transcriptional repressor GATAD2B mediates progesterone receptor suppression of myometrial contractile gene expression.The Journal of biological chemistry · 2017Article
- GR SUMOylation and formation of an SUMO-SMRT/NCoR1-HDAC3 repressing complex is mandatory for GC-induced IR nGRE-mediated transrepression.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- New genetic and physiological factors for excessive erythrocytosis and Chronic Mountain Sickness.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Review
- Article
- Post-translational modifications of the progesterone receptors.The Journal of steroid biochemistry and molecular biology · 2014Review
- Transcriptional repression of estrogen receptor α signaling by SENP2 in breast cancer cells.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Polymorphism of UBC9 gene encoding the SUMO-E2-conjugating enzyme and breast cancer risk.Pathology oncology research : POR · 2014Article
- PIASγ enhanced SUMO-2 modification of Nurr1 activation-function-1 domain limits Nurr1 transcriptional synergy.PloS one · 2013Article
- Small-molecule hormones: molecular mechanisms of action.International journal of endocrinology · 2013Article
- Article
- Role of nuclear progesterone receptor isoforms in uterine pathophysiology.Human reproduction updateReview
- Targeting the sumoylation pathway in cancer stem cells.Molecular & cellular oncologyArticle
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCovalent modification of nuclear receptors by the Small Ubiquitin-like Modifier (SUMO) is dynamically regulated by competing conjugation/deconjugation steps that modulate their overall transcriptional activity. SUMO conjugation of progesterone receptors (PRs) at the N-terminal lysine (K) 388 residue of PR-B is hormone-dependent and suppresses PR-dependent transcription. Mutation of the SUMOylation motif promotes transcriptional synergy.
resultsThe present studies address mechanisms underlying this transcriptional synergy by using SUMOylation deficient PR mutants and PR specifically deSUMOylated by Sentrin-specific proteases (SENPs). We show that deSUMOylation of a small pool of receptors by catalytically competent SENPs globally modulates the cooperativity-driven transcriptional synergy between PR observed on exogenous promoters containing at least two progesterone-response elements (PRE2). This occurs in part by raising PR sensitivity to ligands. The C-terminal ligand binding domain of PR is required for the transcriptional stimulatory effects of N-terminal deSUMOylation, but neither a functional PR dimerization interface, nor a DNA binding domain exhibiting PR specificity, are required.
conclusionWe conclude that direct and reversible SUMOylation of a minor PR protein subpopulation tightly controls the overall transcriptional activity of the receptors at complex synthetic promoters. Transcriptional synergism controlled by SENP-dependent PR deSUMOylation is dissociable from MAPK-catalyzed receptor phosphorylation, from SRC-1 coactivation and from recruitment of histone deacetylases to promoters. This will provide more information for targeting PR as a part of hormonal therapy of breast cancer. Taken together, these data demonstrate that the SUMOylation/deSUMOylation pathway is an interesting target for therapeutic treatment of breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.