ArticleJournal of biomolecular screening2012
Identification and mechanistic studies of a novel ubiquitin E1 inhibitor.
Article in Journal of biomolecular screening, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Targeting the Ubiquitin-Proteasome System for Cancer.MedComm · 2025Review
- Ubiquitination Regulates Reorganization of the Membrane System During Cytomegalovirus Infection.Life (Basel, Switzerland) · 2025Article
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
- A series of xanthenes inhibiting Rad6 function and Rad6-Rad18 interaction in the PCNA ubiquitination cascade.iScience · 2022Article
- Elevated post-ischemic ubiquitination results from suppression of deubiquitinase activity and not proteasome inhibition.Cellular and molecular life sciences : CMLS · 2021Article
- Mode of inhibitory binding of epigallocatechin gallate to the ubiquitin-activating enzyme Uba1RSC advances · 2021Article
- Ubiquitination and the Proteasome as Drug Targets in Trypanosomatid Diseases.Frontiers in chemistry · 2020Review
- Inhibition of the Ubiquitin-Activating Enzyme UBA1 Suppresses Diet-Induced Atherosclerosis in Apolipoprotein E-Knockout Mice.Journal of immunology research · 2020Article
- Differential Inhibition of Human and Trypanosome Ubiquitin E1S by TAK-243 Offers Possibilities for Parasite Selective Inhibitors.Scientific reports · 2019Article
- Multilevel structure-activity profiling reveals multiple green tea compound families that each modulate ubiquitin-activating enzyme and ubiquitination by a distinct mechanism.Scientific reports · 2019Article
- The Epstein-Barr Virus Oncoprotein, LMP1, Regulates the Function of SENP2, a SUMO-protease.Scientific reports · 2019Article
- A patent review of the ubiquitin ligase system: 2015-2018.Expert opinion on therapeutic patents · 2018Review
- Inhibition of ubiquitin-activating enzyme protects against organ injury after intestinal ischemia-reperfusion.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment.Nature medicine · 2018Article
- Proteasome-associated deubiquitinases and cancer.Cancer metastasis reviews · 2017Review
- Domain alternation and active site remodeling are conserved structural features of ubiquitin E1.The Journal of biological chemistry · 2017Article
- Unexpected requirement for a binding partner of the syntaxin family in phagocytosis by murine testicular Sertoli cells.Cell death and differentiation · 2016Article
- Review
- Small-molecule control of intracellular protein levels through modulation of the ubiquitin proteasome system.Angewandte Chemie (International ed. in English) · 2014Review
- High-throughput screening AlphaScreen assay for identification of small-molecule inhibitors of ubiquitin E3 ligase SCFSkp2-Cks1.Journal of biomolecular screening · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Protein degradation via the ubiquitin-proteasome pathway is important for a diverse number of cellular processes ranging from cell signaling to development. Disruption of the ubiquitin pathway occurs in a variety of human diseases, including several cancers and neurological disorders. Excessive proteolysis of tumor suppressor proteins, such as p27, occurs in numerous aggressive human tumors. To discover small-molecule inhibitors that potentially prevent p27 degradation, we developed a series of screening assays, including a cell-based screen of a small-molecule compound library and two novel nucleotide exchange assays. Several small-molecule inhibitors, including NSC624206, were identified and subsequently verified to prevent p27 ubiquitination in vitro. The mechanism of NSC624206 inhibition of p27 ubiquitination was further unraveled using the nucleotide exchange assays and shown to be due to antagonizing ubiquitin activating enzyme (E1). We determined that NSC624206 and PYR-41, a recently reported inhibitor of ubiquitin E1, specifically block ubiquitin-thioester formation but have no effect on ubiquitin adenylation. These studies reveal a novel E1 inhibitor that targets a specific step of the E1 activation reaction. NSC624206 could, therefore, be potentially useful for the control of excessive ubiquitin-mediated proteolysis in vivo.
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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.