ArticleBlood2010
The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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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
94 citing papers in PubMed, 167 citations in OpenAlex.
- UBA1 drives cell cycle to promote malignancy and serves as a therapeutic target in Ewing Sarcoma.BMC cancer · 2026Article
- Prognostic Impact of UBA1 Expression in Breast Cancer.Journal of Cancer · 2026Article
- Targeting the Ubiquitin-Proteasome System for Cancer.MedComm · 2025Review
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- PERK-Olating Through Cancer: A Brew of Cellular Decisions.Biomolecules · 2025Review
- Multi-omics analysis identifies UBA family as potential pan-cancer biomarkers for tumor prognosis and immune microenvironment infiltration.Frontiers in immunology · 2025Article
- Regulation of ubiquitin-proteasome system and its relative pathways in pancreatic adenocarcinoma.BioImpacts : BI · 2025Review
- Proteolysis targeting chimera (PROTAC)-driven antibody internalization of oncogenic cell surface receptors.Communications biology · 2024Article
- Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.International journal of molecular sciences · 2024Article
- The roles of ubiquitination in AML.Annals of hematology · 2024Review
- The matrix protein of lyssavirus hijacks autophagosome for efficient egress by recruiting NEDD4 through its PPxY motif.Autophagy · 2024Article
- Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes.Nature communications · 2023Article
- UPS: Opportunities and challenges for gastric cancer treatment.Frontiers in oncology · 2023Review
- The roles of protein ubiquitination in tumorigenesis and targeted drug discovery in lung cancer.Frontiers in endocrinology · 2023Review
- Progress in Anticancer Drug Development Targeting Ubiquitination-Related Factors.International journal of molecular sciences · 2022Review
- Article
- Role of circRNA in E3 Modification under Human Disease.Biomolecules · 2022Review
- Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases.International journal of molecular sciences · 2022Review
- A series of xanthenes inhibiting Rad6 function and Rad6-Rad18 interaction in the PCNA ubiquitination cascade.iScience · 2022Article
- GRP78 blockade overcomes intrinsic resistance to UBA1 inhibitor TAK-243 in glioblastoma.Cell death discovery · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
The proteasomal pathway of protein degradation involves 2 discrete steps: ubiquitination and degradation. Here, we evaluated the effects of inhibiting the ubiquitination pathway at the level of the ubiquitin-activating enzyme UBA1 (E1). By immunoblotting, leukemia cell lines and primary patient samples had increased protein ubiquitination. Therefore, we examined the effects of genetic and chemical inhibition of the E1 enzyme. Knockdown of E1 decreased the abundance of ubiquitinated proteins in leukemia and myeloma cells and induced cell death. To further investigate effects of E1 inhibition in malignancy, we discovered a novel small molecule inhibitor, 3,5-dioxopyrazolidine compound, 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione (PYZD-4409). PYZD-4409 induced cell death in malignant cells and preferentially inhibited the clonogenic growth of primary acute myeloid leukemia cells compared with normal hematopoietic cells. Mechanistically, genetic or chemical inhibition of E1 increased expression of E1 stress markers. Moreover, BI-1 overexpression blocked cell death after E1 inhibition, suggesting ER stress is functionally important for cell death after E1 inhibition. Finally, in a mouse model of leukemia, intraperitoneal administration of PYZD-4409 decreased tumor weight and volume compared with control without untoward toxicity. Thus, our work highlights the E1 enzyme as a novel target for the treatment of hematologic malignancies.
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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.