ArticleMolecular and cellular biology2007
Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Transcriptome meta-analysis of lung cancer reveals recurrent aberrations in NRG1 and Hippo pathway genes.Nature communications · 2014Pooled it
- An AI-derived peptide PCa2 suppresses pancreatic cancer growth via modulation of the ErbB/PI3K/AKT/mTOR/MYC signaling axis.Cell communication and signaling : CCS · 2026Article
- Loss of ErbB3 redirects Integrin β1 from early endosomal recycling to secretion in extracellular vesicles.The Journal of cell biology · 2026Article
- Myofibrillar protein accumulation but reduced protein synthesis in PDCD4-depleted myotubes.PloS one · 2026Article
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- USP8-Governed MDA5 Homeostasis Promotes Innate Immunity and Autoimmunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Deubiquitinases in Ovarian Cancer: Role in Drug Resistance and Tumor Aggressiveness.International journal of biological sciences · 2024Review
- RNF41 orchestrates macrophage-driven fibrosis resolution and hepatic regeneration.Science translational medicine · 2023Article
- Cisplatin-induced increase in heregulin 1 and its attenuation by the monoclonal ErbB3 antibody seribantumab in bladder cancer.Scientific reports · 2023Article
- The deubiquitinase USP8 regulates ovarian cancer cell response to cisplatin by suppressing apoptosis.Frontiers in cell and developmental biology · 2022Article
- HER3 expression and MEK activation in non-small-cell lung carcinoma.Lung cancer management · 2021Article
- Neoadjuvant chemotherapy promotes the expression of HER3 in patients with ovarian cancer.Oncology letters · 2020Article
- Regulation of Deubiquitinating Enzymes by Post-Translational Modifications.International journal of molecular sciences · 2020Review
- Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation.OncoTargets and therapy · 2020Article
- Mechanisms of Receptor Tyrosine-Protein Kinase ErbB-3 (ERBB3) Action in Human Neoplasia.The American journal of pathology · 2019Review
- Functional genomic characterization of a synthetic anti-HER3 antibody reveals a role for ubiquitination by RNF41 in the anti-proliferative response.The Journal of biological chemistry · 2019Article
- Estradiol promotes rapid degradation of HER3 in ER-positive breast cancer cell line MCF-7.Biochemistry and biophysics reports · 2018Article
- Clinicopathological and prognostic correlations of HER3 expression and its degradation regulators, NEDD4-1 and NRDP1, in primary breast cancer.BMC cancer · 2018Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The molecular mechanisms underlying epidermal growth factor (EGF) receptor tyrosine kinase down-regulation in response to growth factor binding are coming into focus and involve cbl-mediated receptor ubiquitination followed by lysosomal degradation. However, mechanisms underlying the ligand-stimulated degradation of the related receptor tyrosine kinases of the ErbB family do not involve cbl and remain unexplored. Previous studies have demonstrated that the E3 ubiquitin ligase Nrdp1 contributes to the maintenance of steady-state ErbB3 levels by mediating its growth factor-independent degradation. Here we demonstrate that treatment of cells with the ErbB3 ligand neuregulin-1 (NRG1) stabilizes the deubiquitinating enzyme USP8, which in turn stabilizes Nrdp1. The catalytic activity of USP8 is required for NRG1-induced Nrdp1 stabilization. We provide evidence that Akt-mediated phosphorylation of USP8 threonine residue T907 contributes to USP8 stability. Finally, we demonstrate that Nrdp1 or USP8 knockdown suppresses NRG1-induced ErbB3 ubiquitination and degradation in MCF7 breast cancer cells. We conclude that an NRG1-induced protein stability cascade involving USP8 and Nrdp1 mediates the down-regulation of ErbB3. Our observations raise the possibility that the ligand-induced augmentation of pathways involved in the maintenance of basal levels of receptor tyrosine kinases can contribute to ligand-stimulated down-regulation.
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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.