ArticlePLoS biology2018
Hey1- and p53-dependent TrkC proapoptotic activity controls neuroblastoma growth.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Identification of Crucial Genes Associated With MYCN-Driven Neuroblastoma Based on Single-Cell Analysis and Machine Learning.Cancer medicine · 2025Article
- MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway.Non-coding RNA research · 2023Article
- Caspase Cleavage of Receptor Tyrosine Kinases in the Dependence Receptor Family.Biomolecules & therapeutics · 2023Review
- Virus-Mediated Inhibition of Apoptosis in the Context of EBV-Associated Diseases: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2022Review
- Δ40p53 isoform up-regulates netrin-1/UNC5B expression and potentiates netrin-1 pro-oncogenic activity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- The NOTCH1-HEY1 pathway regulates self-renewal and epithelial-mesenchymal transition of salivary adenoid cystic carcinoma cells.International journal of biological sciences · 2020Article
- Notch pathway: a bistable inducer of biological noise?Cell communication and signaling : CCS · 2019Review
- Differential Clinical Significance of Neurotrophin-3 Expression according to MYCN Amplification and TrkC Expression in Neuroblastoma.Journal of Korean medical science · 2019Article
- Proteolytic cleavages of MET: the divide-and-conquer strategy of a receptor tyrosine kinase.BMB reports · 2019Review
- UPAR silencing reveals its role in neuroblastoma.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neurotrophin-3 (NT-3) receptor tropomyosin receptor kinase C (TrkC/NTRK3) has been described as a dependence receptor and, as such, triggers apoptosis in the absence of its ligand NT-3. This proapoptotic activity has been proposed to confer a tumor suppressor activity to this classic tyrosine kinase receptor (RTK). By investigating interacting partners that might facilitate TrkC-induced cell death, we have identified the basic helix-loop-helix (bHLH) transcription factor Hey1 and importin-α3 (karyopherin alpha 4 [KPNA4]) as direct interactors of TrkC intracellular domain, and we show that Hey1 is required for TrkC-induced apoptosis. We propose here that the cleaved proapoptotic portion of TrkC intracellular domain (called TrkC killer-fragment [TrkC-KF]) is translocated to the nucleus by importins and interacts there with Hey1. We also demonstrate that Hey1 and TrkC-KF transcriptionally silence mouse double minute 2 homolog (MDM2), thus contributing to p53 stabilization. p53 transcriptionally regulates the expression of TrkC-KF cytoplasmic and mitochondrial interactors cofactor of breast cancer 1 (COBRA1) and B cell lymphoma 2-associated X (BAX), which will subsequently trigger the intrinsic pathway of apoptosis. Of interest, TrkC was proposed to constrain tumor progression in neuroblastoma (NB), and we demonstrate in an avian model that TrkC tumor suppressor activity requires Hey1 and p53.
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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.