ArticleProtein science : a publication of the Protein Society2017
Stepwise assembly of functional C-terminal REST/NRSF transcriptional repressor complexes as a drug target.
Article in Protein science : a publication of the Protein Society, 2017. 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.
- The Dynamic Roles of Repressor Element 1-Silencing Transcription Factor (REST): A Double-Edged Sword in Neural Health and Disease.Molecular neurobiology · 2025Review
- REST elevation-dependent chromatin remodeling and alternative Grk6 transcript synthesis hyperactivates Cxcr4-Sdf1 signaling in cerebellar granule cell progenitors.bioRxiv : the preprint server for biology · 2025Article
- LPS-induced neuroinflammation induces changes in the transcriptional profile of members of the CoRest repressive complex in the hippocampus.Molecular biology reports · 2024Article
- The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression.Journal of cancer research and clinical oncology · 2023Article
- Epigenetics and immune cells in medulloblastoma.Frontiers in genetics · 2023Review
- Review
- Structural Organization of Human Full-Length PAR3 and the aPKC-PAR6 Complex.Molecular biotechnology · 2022Article
- Distinct biochemical properties of the class I histone deacetylase complexes.Current opinion in chemical biology · 2022Review
- GFI1 Cooperates with IKZF1/IKAROS to Activate Gene Expression in T-cell Acute Lymphoblastic Leukemia.Molecular cancer research : MCR · 2022Article
- Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.Frontiers in cell and developmental biology · 2022Review
- Epigenetic-Based Therapy-A Prospective Chance for Medulloblastoma Patients' Recovery.International journal of molecular sciences · 2021Review
- The HDAC Inhibitor Domatinostat Promotes Cell-Cycle Arrest, Induces Apoptosis, and Increases Immunogenicity of Merkel Cell Carcinoma Cells.The Journal of investigative dermatology · 2021Article
- Expression of the Neural REST/NRSF-SIN3 Transcriptional Corepressor Complex as a Target for Small-Molecule Inhibitors.Molecular biotechnology · 2021Article
- Bifunctional HDAC Therapeutics: One Drug to Rule Them All?Molecules (Basel, Switzerland) · 2020Review
- News about the Role of the Transcription Factor REST in Neurons: From Physiology to Pathology.International journal of molecular sciences · 2019Review
- The ATPase BRG1/SMARCA4 is a protein interaction platform that recruits BAF subunits and the transcriptional repressor REST/NRSF in neural progenitor cells.Molecular and cellular biochemistry · 2019Article
- Elucidating the mechanism of action of domatinostat (4SC-202) in cutaneous T cell lymphoma cells.Journal of hematology & oncology · 2019Article
- NRSF and Its Epigenetic Effectors: New Treatments for Neurological Disease.Brain sciences · 2018Review
- Modulating the Expression Strength of the Baculovirus/Insect Cell Expression System: A Toolbox Applied to the Human Tumor Suppressor SMARCB1/SNF5.Molecular biotechnology · 2018Article
- Pharmacological inhibition of LSD1 activity blocks REST-dependent medulloblastoma cell migration.Cell communication and signaling : CCS · 2018Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In human cells, thousands of predominantly neuronal genes are regulated by the repressor element 1 (RE1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF). REST/NRSF represses transcription of these genes in stem cells and non-neuronal cells by tethering corepressor complexes. Aberrant REST/NRSF expression and intracellular localization are associated with cancer and neurodegeneration in humans. To date, detailed molecular analyses of REST/NRSF and its C-terminal repressor complex have been hampered largely by the lack of sufficient amounts of purified REST/NRSF and its complexes. Therefore, the aim of this study was to express and purify human REST/NRSF and its C-terminal interactors in a baculovirus multiprotein expression system as individual proteins and coexpressed complexes. All proteins were enriched in the nucleus, and REST/NRSF was isolated as a slower migrating form, characteristic of nuclear REST/NRSF in mammalian cells. Both REST/NRSF alone and its C-terminal repressor complex were functionally active in histone deacetylation and histone demethylation and bound to RE1/neuron-restrictive silencer element (NRSE) sites. Additionally, the mechanisms of inhibition of the small-molecule drugs 4SC-202 and SP2509 were analyzed. These drugs interfered with the viability of medulloblastoma cells, where REST/NRSF has been implicated in cancer pathogenesis. Thus, a resource for molecular REST/NRSF studies and drug development has been established.
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