ArticleNucleic acids research2013
NIPP1 maintains EZH2 phosphorylation and promoter occupancy at proliferation-related target genes.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- RAD51B-EZH2 axis as a potential therapeutic target for TNBC through cell fate conversion.Cell death & disease · 2025Article
- Morphological and transcriptional insights into the role of histone phosphorylation-related genes in early development of the chicken duodenum.Animal bioscience · 2025Article
- Norcantharidin inhibits TOP2A expression via H3K27me3 mediated epigenetic regulation to alleviate the progression of hepatocellular carcinoma.Frontiers in pharmacology · 2025Article
- The molecular basis of cell memory in mammals: The epigenetic cycle.Science advances · 2024Review
- Sut-6/NIPP1 modulates tau toxicity.Human molecular genetics · 2023Article
- The role of forkhead-associated (FHA)-domain proteins in plant biology.Plant molecular biology · 2023Review
- Nuclear Inhibitor of Protein Phosphatase 1 (NIPP1) Regulates CNS Tau Phosphorylation and Myelination During Development.Molecular neurobiology · 2022Article
- Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer.The American journal of pathology · 2021Review
- The Role of Polycomb Group Protein BMI1 in DNA Repair and Genomic Stability.International journal of molecular sciences · 2021Review
- Post-translational modifications of PRC2: signals directing its activity.Epigenetics & chromatin · 2020Review
- Phosphatase Regulator NIPP1 Restrains Chemokine-Driven Skin Inflammation.The Journal of investigative dermatology · 2020Article
- Inhibition of CDK2 reduces EZH2 phosphorylation and reactivates ERα expression in high-grade serous ovarian carcinoma.American journal of cancer research · 2020Article
- CDK2-mediated site-specific phosphorylation of EZH2 drives and maintains triple-negative breast cancer.Nature communications · 2019Article
- Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Protein phosphatases in chromatin structure and function.Biochimica et biophysica acta. Molecular cell research · 2019Review
- The deletion of the protein phosphatase 1 regulator NIPP1 in testis causes hyperphosphorylation and degradation of the histone methyltransferase EZH2.The Journal of biological chemistry · 2018Article
- Identification of the substrate recruitment mechanism of the muscle glycogen protein phosphatase 1 holoenzyme.Science advances · 2018Article
- A substrate-trapping strategy for protein phosphatase PP1 holoenzymes using hypoactive subunit fusions.The Journal of biological chemistry · 2018Article
- Unbiased shRNA screening, using a combination of FACS and high-throughput sequencing, enables identification of novel modifiers of Polycomb silencing.Scientific reports · 2018Article
- The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The histone methyltransferase EZH2 regulates cell proliferation and differentiation by silencing Polycomb group target genes. NIPP1, a nuclear regulator of serine/threonine protein phosphatase 1 (PP1), has been implicated in the regulation of EZH2 occupancy at target loci, but the underlying mechanism is not understood. Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1. Recruited NIPP1 enables the net phosphorylation of EZH2 by inhibiting its dephosphorylation by PP1. Accordingly, a NIPP1-binding mutant of EZH2 is hypophosphorylated, and the knockdown of NIPP1 results in a reduced phosphorylation of endogenous EZH2. Conversely, the loss of PP1 is associated with a hyperphosphorylation of EZH2. A genome-wide promoter-binding profiling in HeLa cells revealed that the NIPP1-binding mutant shows a deficient association with about a third of the Polycomb target genes, and these are enriched for functions in proliferation. Our data identify PP1 as an EZH2 phosphatase and demonstrate that the phosphorylation-regulated association of EZH2 with proliferation-related targets depends on associated NIPP1.
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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.