ArticleLife science alliance2021
CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.
Article in Life science alliance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- RHOB Regulates Apoptosis of Granulosa Cells in Muscovy Duck Follicles via Mitochondrial Pathway.Animals : an open access journal from MDPI · 2026Article
- Machine learning-based insights into circulating autoantibody dynamics and treatment outcomes in patients with NSCLC receiving immune checkpoint inhibitors.Frontiers in immunology · 2025Article
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- Autoantibody Profiling Using Human Autoantigen Protein Array and AlphaScreen.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Gene biomarkers and classifiers for various subtypes of HTLV-1-caused ATLL cancer identified by a combination of differential gene co‑expression and support vector machine algorithms.Medical microbiology and immunology · 2023Article
- Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.Molecular cancer research : MCR · 2023Article
- Evaluation of Cell-Free Synthesized Human Channel Proteins for In Vitro Channel Research.Membranes · 2022Article
- Metastatic profiling of HER2-positive breast cancer cell lines in xenograft models.Clinical & experimental metastasis · 2022Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) phosphorylation drives HER2-positive breast cancer cell proliferation. Enforced activation of phosphatases for those receptors could be a therapeutic option for HER2-positive breast cancers. Here, we report that degradation of an endosomal small GTPase, RhoB, by the ubiquitin ligase complex cullin-3 (CUL3)/KCTD10 is essential for both EGFR and HER2 phosphorylation in HER2-positive breast cancer cells. Using human protein arrays produced in a wheat cell-free protein synthesis system, RhoB-GTP, and protein tyrosine phosphatase receptor type H (PTPRH) were identified as interacting proteins of connector enhancer of kinase suppressor of Ras1 (CNKSR1). Mechanistically, constitutive degradation of RhoB, which is mediated by the CUL3/KCTD10 E3 complex, enabled CNKSR1 to interact with PTPRH at the plasma membrane resulting in inactivation of EGFR phosphatase activity. Depletion of CUL3 or KCTD10 led to the accumulation of RhoB-GTP at the plasma membrane followed by its interaction with CNKSR1, which released activated PTPRH from CNKSR1. This study suggests a mechanism of PTPRH activation through the exclusive binding of RhoB-GTP to CNKSR1.
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