ArticleThe Journal of clinical investigation2017
Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
The trial behind it
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
33 citing papers in PubMed, 50 citations in OpenAlex.
- Invasion of Epicardial-Derived Cells to the Trabeculae Mediated by NFPs-Fgf Signaling Regulates Ventricular Compaction.Circulation. Heart failure · 2026Article
- Mechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation.Nature communications · 2025Article
- A Four Amino Acid Intracellular Motif of VISTA Blocks Growth Receptor Signaling in Cancer Cells to Induce Tumor Suppression.Cancer research · 2025Article
- Crosstalk between MST1-Hippo and Wnt/β-Catenin, Notch, and PI3K/Akt pathways in cardiac physiology and pathology.Journal of physiology and biochemistry · 2025Review
- The effects of YAP/TAZ in cardiomyocytes: a scoping review.Molecular biology reports · 2025Article
- scHiCyclePred: a deep learning framework for predicting cell cycle phases from single-cell Hi-C data using multi-scale interaction information.Communications biology · 2024Article
- SPTAN1/NUMB axis senses cell density to restrain cell growth and oncogenesis through Hippo signaling.The Journal of clinical investigation · 2023Article
- STAT5b is a key effector of NRG-1/ERBB4-mediated myocardial growth.EMBO reports · 2023Article
- Redifferentiated cardiomyocytes retain residual dedifferentiation signatures and are protected against ischemic injury.Nature cardiovascular research · 2023Article
- Endothelial deletion of PTBP1 disrupts ventricular chamber development.Nature communications · 2023Article
- The Adaptor Protein NumbL Is Involved in the Control of Glucolipotoxicity-Induced Pancreatic Beta Cell Apoptosis.International journal of molecular sciences · 2023Article
- Mechanisms underlying the therapeutic effects of cinobufagin in treating melanoma based on network pharmacology, single-cell RNA sequencing data, molecular docking, and molecular dynamics simulation.Frontiers in pharmacology · 2023Article
- Numb regulates Tau levels and prevents neurodegeneration in tauopathy mouse models.Science advances · 2022Article
- Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity-a narrative review.Cardiovascular diagnosis and therapy · 2022Review
- Endogenous expression of Notch pathway molecules in human trabecular meshwork cells.Experimental eye research · 2022Article
- PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle.Circulation · 2022Article
- Mediator complex proximal Tail subunit MED30 is critical for Mediator core stability and cardiomyocyte transcriptional network.PLoS genetics · 2021Article
- Article
- ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration.Nature cell biology · 2020Article
- Exon 3 of theG3 (Bethesda, Md.) · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation. Unexpectedly, activated STAT5 overrode Hippo-mediated inhibition and drove YAP1 to the nucleus. Consequent aberrant cardiomyocyte proliferation resulted in ventricular noncompaction that was markedly rescued by heterozygous loss of function of either ERBB2 or YAP1. Further investigations revealed that NUMB and NUMBL interacted with small GTPase Rab7 to transition ERBB2 from early to late endosome for degradation. Our studies provide insight into mechanisms by which NUMB and NUMBL promote cardiomyocyte cell cycle withdrawal and highlight previously unsuspected connections between pathways that are important for cardiomyocyte cell cycle reentry, with relevance to ventricular noncompaction cardiomyopathy and regenerative medicine.
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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.