ArticleOncogene2012
Acetylation controls Notch3 stability and function in T-cell leukemia.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 58 citations in OpenAlex.
- HDAC inhibition reprograms stem cell fate to suppress infantile hemangioma vasculogenesis.Angiogenesis · 2026Article
- Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- Hdac1 and Hdac2 positively regulate Notch1 gain-of-function pathogenic signaling in committed osteoblasts of male mice.Birth defects research · 2024Article
- Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.Frontiers in oncology · 2024Review
- Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification.Biomolecules · 2023Review
- Notch-Signaling Deregulation Induces Myeloid-Derived Suppressor Cells in T-Cell Acute Lymphoblastic Leukemia.Frontiers in immunology · 2022Article
- Bruceine H Mediates EGFR-TKI Drug Persistence in NSCLC by Notch3-Dependent β-Catenin Activating FOXO3a Signaling.Frontiers in oncology · 2022Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Article
- The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies.Frontiers in molecular biosciences · 2021Review
- Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma.Clinical epigenetics · 2020Review
- HDAC3 functions as a positive regulator in Notch signal transduction.Nucleic acids research · 2020Article
- Notch3 in Development, Health and Disease.Biomolecules · 2020Review
- Making sense out of missense mutations: Mechanistic dissection of Notch receptors through structure-function studies in Drosophila.Development, growth & differentiation · 2020Review
- NF-κB1 Regulates Immune Environment and Outcome of Notch-Dependent T-Cell Acute Lymphoblastic Leukemia.Frontiers in immunology · 2020Article
- Recent Update of HDAC Inhibitors in Lymphoma.Frontiers in cell and developmental biology · 2020Review
- Decoding the PTM-switchboard of Notch.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Protein Expression Analysis in Uterine Cervical Cancer for Potential Targets in Treatment.Pathology oncology research : POR · 2019Article
- Histone Deacetylases (HDACs) Guided Novel Therapies for T-cell lymphomas.International journal of medical sciences · 2019Review
- The Role ofThe oncologist · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-translational modifications of Notch3 and their functional role with respect to Notch3 overexpression in T-cell leukemia are still poorly understood. We identify here a specific novel property of Notch3 that is acetylated and deacetylated at lysines 1692 and 1731 by p300 and HDAC1, respectively, a balance impaired by HDAC inhibitors (HDACi) that favor hyperacetylation. By using HDACi and a non-acetylatable Notch3 mutant carrying K/R(1692-1731) mutations in the intracellular domain, we show that Notch3 acetylation primes ubiquitination and proteasomal-mediated degradation of the protein. As a consequence, Notch3 protein expression and its transcriptional activity are decreased both in vitro and in vivo in Notch3 transgenic (tg) mice, thus impairing downstream signaling upon target genes. Consistently, Notch3-induced T-cell proliferation is inhibited by HDACi, whereas it is enhanced by the non-acetylatable Notch3-K/R(1692-1731) mutant. Finally, HDACi-induced Notch3 hyperacetylation prevents in vivo growth of T-cell leukemia/lymphoma in Notch3 tg mice. Together, our findings suggest a novel level of Notch signaling control in which Notch3 acetylation/deacetylation process represents a key regulatory switch, thus representing a suitable druggable target for Notch3-sustained T-cell acute lymphoblastic leukemia therapy.
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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.