ArticleMolecular endocrinology (Baltimore, Md.)2010
The progesterone receptor hinge region regulates the kinetics of transcriptional responses through acetylation, phosphorylation, and nuclear retention.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Placental Steroid Hormones in Preeclampsia: Multilayered Regulation of Endocrine Pathogenesis.Endocrine reviews · 2026Review
- PPARγ acetylation governs mammary adenocarcinoma tumor growth via acetylated residues that determine DNA sequence-specific binding.Oncogene · 2025Article
- Advances in the molecular mechanisms underlying progestin resistance in endometrial cancer.Fundamental research · 2025Review
- Progesterone (P4) ameliorates cigarette smoke-induced chronic obstructive pulmonary disease (COPD).Molecular medicine (Cambridge, Mass.) · 2024Article
- P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Progesterone Attenuates SIRT1-Deficiency-Mediated Pre-Eclampsia.Biomolecules · 2022Article
- Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.Cancers · 2021Review
- Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers · 2021Review
- Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome.International journal of molecular sciences · 2021Review
- 90 YEARS OF PROGESTERONE: Steroid receptors as MAPK signaling sensors in breast cancer: let the fates decide.Journal of molecular endocrinology · 2020Review
- PRMT1 Is Critical for the Transcriptional Activity and the Stability of the Progesterone Receptor.iScience · 2020Article
- Progesterone Receptor Gene Variants in Metastatic Estrogen Receptor Positive Breast Cancer.Hormones & cancer · 2020Article
- The Versatility of Sirtuin-1 in Endocrinology and Immunology.Frontiers in cell and developmental biology · 2020Review
- Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy.Nature communications · 2019Article
- SUMOylation Regulates Transcription by the Progesterone Receptor A Isoform in a Target Gene Selective Manner.Diseases (Basel, Switzerland) · 2018Article
- RNPC1 enhances progesterone receptor functions by regulating its mRNA stability in breast cancer.Oncotarget · 2017Article
- Fibroblast growth factor signalling induces loss of progesterone receptor in breast cancer cells.Oncotarget · 2016Article
- Article
- Lysine deacetylase inhibition attenuates hypertension and is accompanied by acetylation of mineralocorticoid receptor instead of histone acetylation in spontaneously hypertensive rats.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
- Modifications to glucocorticoid and progesterone receptors alter cell fate in breast cancer.Journal of molecular endocrinology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Progesterone receptors (PRs) are critical regulators of mammary gland development and contributors to breast cancer progression. Posttranslational modifications of PR have been shown to alter hormone responsiveness. Site-directed mutagenesis demonstrated that upon hormone binding, PR is acetylated at the consensus sequence, KXKK (amino acids 638-641), located within the hinge region. We created an acetylation-deficient (K-A) mutant as well as acetylation mimics (K-Q or K-T). Interestingly, similar to K-A PR, PR acetylation mimics (K-Q or K-T) displayed delayed phosphorylation and nuclear entry relative to wild-type (wt) PR-B, indicative of disruption of PR nuclear-cytoplasmic shuttling. Wt PR-B, but not K-mutant PRs, induced c-myc at 1 h of progestin treatment. However, at 6 h of treatment, c-myc induction was comparable with levels induced by wt PR-B, suggesting that the precise timing of PR phosphorylation and nuclear retention are critical for cells to rapidly initiate robust transcriptional programs. In contrast to c-myc, progestin-induced serum- and glucocorticoid-regulated kinase (SGK) expression displayed sensitivity to PR acetylation but not nuclear entry. Namely, in the presence of progestin, acetylation-deficient (K-A) mutant PR-B up-regulated SGK mRNA relative to wt PR; progesterone response element-luciferase assays confirmed this result. However, K-Q and K-T acetylation mimics only weakly induced SGK expression independently of nuclear retention. These data reveal the ability of PR acetylation to alter the magnitude of transcriptional response at selected (slow response) promoters (SGK), whereas the hinge region dictates the kinetics of the transcriptional response to hormone at other (rapid response) promoters (c-myc). In sum, the PR hinge region is multifunctional. Understanding the ability of this region to couple acetylation, phosphorylation, and nuclear entry may provide clues to mechanisms of altered hormone responsiveness.
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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.