ArticleBiochemistry2011
Targeting a DNA binding motif of the EVI1 protein by a pyrrole-imidazole polyamide.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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, 33 citations in OpenAlex.
- MECOM Function Is Critical for AR-Driven Treatment-Resistant Prostate Cancer.Cancer research · 2026Article
- Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.Nature genetics · 2024Article
- Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML.Nature communications · 2024Article
- Article
- Internalization of Foldamer-Based DNA Mimics through a Site-Specific Antibody Conjugate to Target HER2-Positive Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- PAX8 and MECOM are interaction partners driving ovarian cancer.Nature communications · 2021Article
- Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: artificial analogues of DNA mimic proteins.Nucleic acids research · 2019Article
- EVI1 overexpression reprograms hematopoiesis via upregulation of Spi1 transcription.Nature communications · 2018Article
- Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression.Scientific reports · 2018Article
- ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer.Molecules (Basel, Switzerland) · 2018Review
- Targeting Transcription Factors for Cancer Treatment.Molecules (Basel, Switzerland) · 2018Review
- Article
- Systematic synthetic and biophysical development of mixed sequence DNA binding agents.Organic & biomolecular chemistry · 2017Article
- EVI1 Interferes with Myeloid Maturation via Transcriptional Repression of Cebpa, via Binding to Two Far Downstream Regulatory Elements.The Journal of biological chemistry · 2016Article
- Pyrrole-imidazole polyamide targeted to break fusion sites in TMPRSS2 and ERG gene fusion represses prostate tumor growth.Cancer science · 2014Article
- Novel genetic targets in endometrial cancer.Expert opinion on therapeutic targets · 2014Article
- Structure-dependent inhibition of the ETS-family transcription factor PU.1 by novel heterocyclic diamidines.Nucleic acids research · 2014Article
- Article
- Targeting the DNA-binding activity of the human ERG transcription factor using new heterocyclic dithiophene diamidines.Nucleic acids research · 2013Article
- Cell interactions and patterned intercalations shape and link epithelial tubes in C. elegans.PLoS genetics · 2013Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The zinc finger protein EVI1 is causally associated with acute myeloid leukemogenesis, and inhibition of its function with a small molecule therapeutic may provide effective therapy for EVI1-expressing leukemias. In this paper we describe the development of a pyrrole-imidazole polyamide to specifically block EVI1 binding to DNA. We first identify essential domains for leukemogenesis through structure-function studies on both EVI1 and the t(3;21)(q26;q22)-derived RUNX1-MDS1-EVI1 (RME) protein, which revealed that DNA binding to the cognate motif GACAAGATA via the first of two zinc finger domains (ZF1, encompassing fingers 1-7) is essential transforming activity. To inhibit DNA binding via ZF1, we synthesized a pyrrole-imidazole polyamide 1, designed to bind to a subsite within the GACAAGATA motif and thereby block EVI1 binding. DNase I footprinting and electromobility shift assays revealed a specific and high affinity interaction between polyamide 1 and the GACAAGATA motif. In an in vivo CAT reporter assay using NIH-3T3-derived cell line with a chromosome-embedded tet-inducible EVI1-VP16 as well as an EVI1-responsive reporter, polyamide 1 completely blocked EVI1-responsive reporter activity. Growth of a leukemic cell line bearing overexpressed EVI1 was also inhibited by treatment with polyamide 1, while a control cell line lacking EVI1 was not. Finally, colony formation by RME was attenuated by polyamide 1 in a serial replating assay. These studies provide evidence that a cell permeable small molecule may effectively block the activity of a leukemogenic transcription factor and provide a valuable tool to dissect critical functions of EVI1 in leukemogenesis.
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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.