ArticleACS chemical biology2011
Selective inactivation of a human neuronal silencing phosphatase by a small molecule inhibitor.
Article in ACS chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Tracking Inhibition of Human Small C-Terminal Domain Phosphatase 1 Using 193 nm Ultraviolet Photodissociation Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Identification of Inhibitors of the Disease-Associated Protein Phosphatase Scp1 Using Antibody Mimetic Molecules.International journal of molecular sciences · 2024Article
- Glycolytic flux control by drugging phosphoglycolate phosphatase.Nature communications · 2022Article
- Targeted Covalent Inhibition of Small CTD Phosphatase 1 to Promote the Degradation of the REST Transcription Factor in Human Cells.Journal of medicinal chemistry · 2022Article
- Osteoarthritis-Related Inflammation Blocks TGF-β's Protective Effect on Chondrocyte Hypertrophy via (de)Phosphorylation of the SMAD2/3 Linker Region.International journal of molecular sciences · 2021Article
- Targeting the C-Terminal Domain Small Phosphatase 1.Life (Basel, Switzerland) · 2020Review
- Article
- Phosphatase activity of small C-terminal domain phosphatase 1 (SCP1) controls the stability of the key neuronal regulator RE1-silencing transcription factor (REST).The Journal of biological chemistry · 2018Article
- Characterization of hydrogen bonding motifs in proteins: hydrogen elimination monitoring by ultraviolet photodissociation mass spectrometry.Physical chemistry chemical physics : PCCP · 2017Article
- Two-track virtual screening approach to identify both competitive and allosteric inhibitors of human small C-terminal domain phosphatase 1.Journal of computer-aided molecular design · 2017Article
- Phosphatase UBLCP1 controls proteasome assembly.Open biology · 2017Article
- Dephosphorylating eukaryotic RNA polymerase II.Biochimica et biophysica acta · 2016Review
- A potent and selective inhibitor for the UBLCP1 proteasome phosphatase.Bioorganic & medicinal chemistry · 2015Article
- Panoramic view of a superfamily of phosphatases through substrate profiling.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Allosteric inhibitors of the Eya2 phosphatase are selective and inhibit Eya2-mediated cell migration.The Journal of biological chemistry · 2014Article
- Cross-talk of phosphorylation and prolyl isomerization of the C-terminal domain of RNA Polymerase II.Molecules (Basel, Switzerland) · 2014Review
- Viewing serine/threonine protein phosphatases through the eyes of drug designers.The FEBS journal · 2013Review
- Identification of novel PTPRQ phosphatase inhibitors based on the virtual screening with docking simulations.Theoretical biology & medical modelling · 2013Article
- UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The unstructured C-terminal domain (CTD) of eukaryotic RNA polymerase II dynamically regulates the process of transcription by recruiting different factors to nascent mRNA through its multiple phosphorylation patterns. A newly discovered class of phosphatases, the human small C-terminal domain phosphatases (Scp's), specifically dephosphorylates phosphorylated Ser(5) (phospho.Ser5) of the tandem heptad repeats of the CTD of RNA polymerase II. Scp's also function as transcription regulators that epigenetically silence the expression of specific neuronal genes, whose inactivation leads to neuronal stem cell differentiation. Small molecule inhibitors of Scp's will be valuable for elucidating their mechanism in nervous system development and can possibly offer new strategies to treat diseases related to neurodegeneration. Despite the difficulty in developing selective inhibitors of protein phosphatases, we have recognized a characteristic hydrophobic binding pocket adjacent to the active site in Scp's that may facilitate selective inhibition. In the present study, we successfully identified the first selective lead compound, rabeprazole, for the Scp/TFIIF-interacting CTD phosphatase (Fcp) family. The high-resolution crystal structure of rabeprazole-bound Scp1 showed that the compound indeed binds to the hydrophobic binding pocket. We further confirmed that rabeprazole only targets Scp's but not its close family members Fcp1 and Dullard or bacteriophage λ Ser/Thr phosphatase. Such specificity may prove important for In Vivo studies since accidental inhibition of Fcp1 or Dullard would result in cell malfunctions and even cell death.
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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.