ArticleThe Journal of biological chemistry2014
Lysine methylation of progesterone receptor at activation function 1 regulates both ligand-independent activity and ligand sensitivity of the receptor.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Ligand-Dependent and -Independent Functions of Activation Function 1 of Progesterone Receptor in Genome-Wide Gene Regulation and in Cell Proliferation and Apoptosis of Breast Cancer Cells.International journal of molecular sciences · 2026Article
- Dynamic Arginine Methylation of YBX1 Relay Controls Its Phase Separation and Chemoradiotherapy Resistance in Rectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- KDM4A serves as an α-tubulin demethylase regulating microtubule polymerization and cell mitosis.Science advances · 2025Article
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Tau Lysine Pseudomethylation Regulates Microtubule Binding and Enhances Prion-like Tau Aggregation.International journal of molecular sciences · 2023Article
- Activation function 1 of progesterone receptor is required for progesterone antagonism of oestrogen action in the uterus.BMC biology · 2022Article
- Activation function 1 of progesterone receptor is required for mammary development and regulation of RANKL during pregnancy.Scientific reports · 2022Article
- How Protein Methylation Regulates Steroid Receptor Function.Endocrine reviews · 2022Review
- Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.Cancers · 2021Review
- α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation.Nature communications · 2021Article
- 90 YEARS OF PROGESTERONE: Molecular mechanisms of progesterone receptor action on the breast cancer genome.Journal of molecular endocrinology · 2020Review
- Sex-specific Tau methylation patterns and synaptic transcriptional alterations are associated with neural vulnerability during chronic neuroinflammation.Journal of autoimmunity · 2019Article
- Dependence of Chromatosome Structure on Linker Histone Sequence and Posttranslational Modification.Biophysical journal · 2018Article
- 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
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progesterone receptor (PR) exists in two isoforms, PRA and PRB, and both contain activation functions AF-1 and AF-2. It is believed that AF-1 is primarily responsible for the ligand-independent activity, whereas AF-2 mediates ligand-dependent PR activation. Although more than a dozen post-translational modifications of PR have been reported, no post-translational modification on AF-1 or AF-2 has been reported. Using LC-MS/MS-based proteomic analysis, this study revealed AF-1 monomethylation at Lys-464. Mutational analysis revealed the remarkable importance of Lys-464 in regulating PR activity. Single point mutation K464Q or K464A led to ligand-independent PR gel upshift similar to the ligand-induced gel upshift. This upshift was associated with increases in both ligand-dependent and ligand-independent PR phosphorylation and PR activity due to the hyperactivation of AF-1. In contrast, mutation of Lys-464 to the bulkier phenylalanine to mimic the effect of methylation caused a drastic decrease in PR activity. Importantly, PR-K464Q also showed heightened ligand sensitivity, and this was associated with increases in its functional interaction with transcription co-regulators NCoR1 and SRC-1. These results suggest that monomethylation of PR at Lys-464 probably has a repressive effect on AF-1 activity and ligand sensitivity.
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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.