ArticleProceedings of the National Academy of Sciences of the United States of America2019
PTEN arginine methylation by PRMT6 suppresses PI3K-AKT signaling and modulates pre-mRNA splicing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration-A Systemic Review.International journal of molecular sciences · 2022Pooled it
- Arginine Methylation in Alternative Splicing: Implications for Cancer Therapy.Journal of cellular physiology · 2026Review
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease.Biology · 2025Review
- Methylation of RBM39 by PRMT6 enhances resistance to Indisulam in non-small cell lung cancer by promoting alternative splicing of proto-oncogenes.PLoS biology · 2025Article
- Assessment of PRMT6-dependent alternative splicing in pluripotent and differentiating NT2/D1 cells.Life science alliance · 2025Article
- PRMT7-Mediated PTEN Activation Enhances Bone Regeneration in Female Mice.International journal of molecular sciences · 2025Article
- Protein arginine methyltransferase 6 enhances immune checkpoint blockade efficacy via the STING pathway in MMR-proficient colorectal cancer.Journal for immunotherapy of cancer · 2025Article
- Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase (G6PD) by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis.Science China. Life sciences · 2024Article
- PRMT6-mediated transcriptional activation of ythdf2 promotes glioblastoma migration, invasion, and emt via the wnt-β-catenin pathway.Journal of experimental & clinical cancer research : CR · 2024Article
- Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men.iScience · 2024Article
- The Role of Protein Methyltransferases in Immunity.Molecules (Basel, Switzerland) · 2024Review
- Critical Roles of Protein Arginine Methylation in the Central Nervous System.Molecular neurobiology · 2023Review
- PRMT1 and PRMT5: on the road of homologous recombination and non-homologous end joining.Genome instability & disease · 2023Article
- The PRMT6/PARP1/CRL4B Complex Regulates the Circadian Clock and Promotes Breast Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- PRMT7 Inhibits the Proliferation and Migration of Gastric Cancer Cells by Suppressing the PI3K/AKT Pathway via PTEN.Journal of Cancer · 2023Article
- Chemical and structural approaches to investigate PTEN function and regulation.Methods in enzymology · 2023Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Arginine methylation in the epithelial-to-mesenchymal transition.The FEBS journal · 2022Review
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arginine methylation is a ubiquitous posttranslational modification that regulates critical cellular processes including signal transduction and pre-mRNA splicing. Here, we report that the tumor-suppressor PTEN is methylated by protein arginine methyltransferase 6 (PRMT6). Mass-spectrometry analysis reveals that PTEN is dimethylated at arginine 159 (R159). We found that PTEN is mutated at R159 in cancers, and the PTEN mutant R159K loses its capability to inhibit the PI3K-AKT cascade. Furthermore, PRMT6 is physically associated with PTEN, promotes asymmetrical dimethylation of PTEN, and regulates the PI3K-AKT cascade through PTEN R159 methylation. In addition, using transcriptome analyses, we found that PTEN R159 methylation is involved in modulation of pre-mRNA alternative splicing. Our results demonstrate that PTEN is functionally regulated by arginine methylation. We propose that PTEN arginine methylation modulates pre-mRNA alternative splicing and influences diverse physiologic processes.
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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.