ArticleMolecular and cellular biology2004
Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
78 citing papers in PubMed, 131 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Preoperative onapristone-XR in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer: SOLTI-1802 ONAWA trial results.NPJ breast cancer · 2026Article
- Split Decisions in Hormone Signaling: Distinct Roles for Progesterone Receptor Isoforms in Breast Cancer Biology.Endocrinology · 2025Review
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- P129, a pyrazole ring-containing isolongifolanone-derivate: synthesis and investigation of anti-glioma action mechanism.Discover oncology · 2024Article
- A molecular toolbox to study progesterone receptor signaling.Journal of mammary gland biology and neoplasia · 2023Article
- Article
- How Protein Methylation Regulates Steroid Receptor Function.Endocrine reviews · 2022Review
- Structure-Based Design of 2-Aminopurine Derivatives as CDK2 Inhibitors for Triple-Negative Breast Cancer.Frontiers in pharmacology · 2022Article
- A set of accessible enhancers enables the initial response of breast cancer cells to physiological progestin concentrations.Nucleic acids research · 2021Article
- What Do We Know about Classical and Non-Classical Progesterone Receptors in the Human Female Reproductive Tract? A Review.International journal of molecular sciences · 2021Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer.British journal of cancer · 2021Article
- Progesterone Receptor Together with PKCα Expression as Prognostic Factors for Astrocytomas Malignancy.OncoTargets and therapy · 2021Article
- 90 YEARS OF PROGESTERONE: Steroid receptors as MAPK signaling sensors in breast cancer: let the fates decide.Journal of molecular endocrinology · 2020Review
- Progesterone receptor isoform B expression in pulmonary neuroendocrine cells decreases cell proliferation.The Journal of steroid biochemistry and molecular biology · 2019Article
- Progesterone Receptor Attenuates STAT1-Mediated IFN Signaling in Breast Cancer.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Progesterone impairs Herceptin effect on breast cancer cells.Oncology letters · 2018Article
- Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs.Journal of hematology & oncology · 2017Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Human progesterone receptors (PR) are phosphorylated by cyclin-dependent protein kinase 2 (CDK2) at multiple sites, including Ser400. Herein, we have addressed the significance of phosphorylation of this residue. PR phospho-Ser400-specific antibodies revealed regulated phosphorylation of Ser400 in response to progestins and mitogens, and this correlated with increased CDK2 levels and activity. Expression of cyclin E elevated CDK2 activity and downregulated PR independently of ligand. Similarly, overexpression of activated mutant CDK2 increased PR transcriptional activity in the absence and presence of progestin. Mutation of PR Ser400 to alanine (S400A) blocked CDK2-induced PR activity in the absence, but not in the presence, of progestin. PR was unresponsive to activated CDK2 in breast cancer cells with elevated p27, and RNA interference knock-down of p27 partially restored CDK2-induced ligand-independent PR activation. Similarly, in p27(-/-) mouse embryonic fibroblasts, elevated CDK2 activity increased wild-type (wt) but not S400A PR transcriptional activity in the absence of progestin. CDK2 induced nuclear localization of unliganded wt but not S400A PR; liganded S400A PR exhibited delayed nuclear accumulation. These studies demonstrate that CDK2 regulates PR in the absence of progestins via phosphorylation of Ser400, thus revealing a novel mechanism for upregulated PR transcriptional activity in human breast cancer cells expressing altered cell cycle regulatory molecules.
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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.