ArticleThe EMBO journal2005
Targeting fusion protein/corepressor contact restores differentiation response in leukemia cells.
Article in The EMBO journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 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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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
13 citing papers in PubMed, 37 citations in OpenAlex.
- Defined Human Leukemic CD34+ Liquid Cultures to Study HDAC/Transcriptional Repressor Complexes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Nuclear export of chimeric mRNAs depends on an lncRNA-triggered autoregulatory loop in blood malignancies.Cell death & disease · 2020Article
- Review
- The nuclear receptor corepressor NCoR1 regulates hematopoiesis and leukemogenesis in vivo.Blood advances · 2019Article
- Article
- Unlocking the potential of retinoic acid in anticancer therapy.British journal of cancer · 2014Review
- Nuclear receptor corepressor complexes in cancer: mechanism, function and regulation.American journal of clinical and experimental urology · 2014Review
- Interference with RUNX1/ETO leukemogenic function by cell-penetrating peptides targeting the NHR2 oligomerization domain.BioMed research international · 2013Article
- Targeting the acute promyelocytic leukemia-associated fusion proteins PML/RARα and PLZF/RARα with interfering peptides.PloS one · 2012Article
- Vitamin D3-driven signals for myeloid cell differentiation--implications for differentiation therapy.Leukemia research · 2010Review
- Article
- HDAC3: taking the SMRT-N-CoRrect road to repression.Oncogene · 2007Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AML1/ETO and PML/RARalpha leukemia fusion proteins induce acute myeloid leukemia by acting as transcriptional repressors. They interact with corepressors, such as N-CoR and SMRT, that recruit a multiprotein complex containing histone deacetylases on crucial myeloid differentiation genes. This leads to gene repression contributing to generate a differentiation block. We expressed in leukemia cells containing PML/RARalpha and AML1/ETO N-CoR protein fragments derived from fusion protein/corepressor interaction surfaces. This blocks N-CoR/SMRT binding by these fusion proteins, and disrupts the repressor protein complex. In consequence, the expression of genes repressed by these fusion proteins increases and differentiation response to vitamin D3 and retinoic acid is restored in previously resistant cells. The alteration of PML/RARalpha-N-CoR/SMRT connections triggers proteasomal degradation of the fusion protein. The N-CoR fragments are biologically effective also when directly transduced by virtue of a protein transduction domain. Our data indicate that fusion protein activity is permanently required to maintain the leukemia phenotype and show the route to developing a novel therapeutic approach for leukemia, based on its molecular pathogenesis.
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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.