ArticleNucleic acids research2018
PHD finger protein 1 (PHF1) is a novel reader for histone H4R3 symmetric dimethylation and coordinates with PRMT5-WDR77/CRL4B complex to promote tumorigenesis.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 83 citations in OpenAlex.
- CD19-targeting CAR T cell immunotherapy outcomes correlate with genomic modification by vector integration.The Journal of clinical investigation · 2020Trial
- Emerging role of protein arginine methyltransferase 5 in gastrointestinal cancer (Review).Oncology letters · 2026Review
- PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition.Research (Washington, D.C.) · 2026Article
- Protein arginine methyltransferase 5 as a novel therapeutic target in solid tumors.Genes & diseases · 2026Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- RNF187 Facilitates Proliferation and Migration of Human Spermatogonial Stem Cells Through WDR77 Polyubiquitination.Cell proliferation · 2025Article
- Emerging roles of protein arginine methyltransferase in multiple myeloma.Molecular therapy. Oncology · 2025Review
- TBL2 Promotes Tumorigenesis via PRMT5/WDR77-Mediated AKT Activation in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- Role of PRMT1 and PRMT5 in Breast Cancer.International journal of molecular sciences · 2024Review
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Epigenetic regulation of breast cancer metastasis.Cancer metastasis reviews · 2024Review
- SMYD4 monomethylates PRMT5 and forms a positive feedback loop to promote hepatocellular carcinoma progression.Cancer science · 2024Article
- Dysregulation of arginine methylation in tumorigenesis.Frontiers in molecular biosciences · 2024Review
- FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.Frontiers in pharmacology · 2024Review
- Deciphering the dual roles of PHD finger proteins from oncogenic drivers to tumor suppressors.Frontiers in cell and developmental biology · 2024Review
- Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2.Genes · 2023Review
- PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.Cell death & disease · 2023Article
- Research progress on PRMTs involved in epigenetic modification and tumour signalling pathway regulation (Review).International journal of oncology · 2023Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. PHF1 [plant homeodomain (PHD) finger protein 1], which contains two kinds of histone reader modules, a Tudor domain and two PHD fingers, is an essential factor for epigenetic regulation and genome maintenance. While significant progress has been made in characterizing the function of the Tudor domain, the roles of the two PHD fingers are poorly defined. Here, we demonstrated that the N-terminal PHD finger of PHF1 recognizes symmetric dimethylation of H4R3 (H4R3me2s) catalyzed by PRMT5-WDR77. However, the C-terminal PHD finger of PHF1, instead of binding to modified histones, directly interacts with DDB1, the main component of the CUL4B-Ring E3 ligase complex (CRL4B), which is responsible for H2AK119 mono-ubiquitination (H2AK119ub1). We showed that PHF1, PRMT5-WDR77, and CRL4B reciprocally interact with one another and collaborate as a functional unit. Genome-wide analysis of PHF1/PRMT5/CUL4B targets identified a cohort of genes including E-cadherin and FBXW7, which are critically involved in cell growth and migration. We demonstrated that PHF1 promotes cell proliferation, invasion, and tumorigenesis in vivo and in vitro and found that its expression is markedly upregulated in a variety of human cancers. Our data identified a new reader for H4R3me2s and provided a molecular basis for the functional interplay between histone arginine methylation and ubiquitination. The results also indicated that PHF1 is a key factor in cancer progression, supporting the pursuit of PHF1 as a target for cancer therapy.
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