ArticleMolecular and cellular biology2007
The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are regulated by CARM1-dependent methylation.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 130 citations in OpenAlex.
- Small-Molecule Activators of PRMT1: Discovery, SAR Analyses, and Proapoptotic Effects in Pancreatic Cancer Cells.Journal of medicinal chemistry · 2026Article
- The ULK1-NCOA3 axis restrains de novo lipogenesis and prevents diet-induced steatohepatitis and fibrosis in mice.The Journal of clinical investigation · 2026Article
- A suite of macrocyclic peptide inhibitors and substrate probes for arginine methyltransferases.Chemical science · 2026Article
- Nuclear receptor coregulator interactions: beyond the switch.Genes & development · 2026Review
- Multifaceted roles of CARM1 beyond histone arginine methylation.Experimental & molecular medicine · 2025Review
- Emerging roles of protein arginine methyltransferase in multiple myeloma.Molecular therapy. Oncology · 2025Review
- The emerging role of CARM1 in cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- NCOA3 knockdown delays human embryo development.Heliyon · 2024Article
- CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development.Nucleic acids research · 2024Article
- Protein Arginine Methyltransferase CARM1 in Human Breast Cancer.Endocrinology · 2024Review
- p160 nuclear receptor coactivator family members and their role in rare fusion‑driven neoplasms (Review).Oncology letters · 2024Review
- Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity.Nature communications · 2024Article
- Article
- Control of protein stability by post-translational modifications.Nature communications · 2023Review
- Protein arginine methylation in transcription and epigenetic regulation.Frontiers in epigenetics and epigenomics · 2023Review
- AIB1/SRC-3/NCOA3 function in estrogen receptor alpha positive breast cancer.Frontiers in endocrinology · 2023Review
- How Protein Methylation Regulates Steroid Receptor Function.Endocrine reviews · 2022Review
- Methylation of dual-specificity phosphatase 4 controls cell differentiation.Cell reports · 2021Article
- Article
- Transcriptional regulation by methyltransferases and their role in the heart: highlighting novel emerging functionality.American journal of physiology. Heart and circulatory physiology · 2020Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The transcriptional coactivator p/CIP(SRC-3/AIB1/ACTR/RAC3) binds liganded nuclear hormone receptors and facilitates transcription by directly recruiting accessory factors such as acetyltransferase CBP/p300 and the coactivator arginine methyltransferase CARM1. In the present study, we have established that recombinant p/CIP (p300/CBP interacting protein) is robustly methylated by CARM1 in vitro but not by other protein arginine methyltransferase family members. Metabolic labeling of MCF-7 breast cancer cells with S-adenosyl-L-[methyl-(3)H]methionine and immunoblotting using dimethyl arginine-specific antibodies demonstrated that p/CIP is specifically methylated in intact cells. In addition, methylation of full-length p/CIP is not supported by extracts derived from CARM1(-/-) mouse embryo fibroblasts, indicating that CARM1 is required for p/CIP methylation. Using mass spectrometry, we have identified three CARM1-dependent methylation sites located in a glutamine-rich region within the carboxy terminus of p/CIP which are conserved among all steroid receptor coactivator proteins. These results were confirmed by in vitro methylation of p/CIP using carboxy-terminal truncation mutants and synthetic peptides as substrates for CARM1. Analysis of methylation site mutants revealed that arginine methylation causes an increase in full-length p/CIP turnover as a result of enhanced degradation. Additionally, methylation negatively impacts transcription via a second mechanism by impairing the ability of p/CIP to associate with CBP. Collectively, our data highlight coactivator methylation as an important regulatory mechanism in hormonal signaling.
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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.