ArticleInternational journal of molecular sciences2021
Linear Ubiquitination Mediates EGFR-Induced NF-κB Pathway and Tumor Development.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 25 citations in OpenAlex.
- M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress.Cell death and differentiation · 2026Article
- 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
- Reversible surface modifications of functional proteins for accelerated cytosolic delivery via cell-penetrating peptide clusters.Nature communications · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Mechanistic insights into triclosan-induced hepatotoxicity: A network toxicology and molecular docking approach.PloS one · 2026Article
- Mechanistic insights of lenvatinib: enhancing cisplatin sensitivity, inducing apoptosis, and suppressing metastasis in bladder cancer cells through EGFR/ERK/P38/NF-κB signaling inactivation.Cancer cell international · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- High TNF and NF-κB Pathway Dependency Are Associated with AZD5582 Sensitivity in OSCC via CASP8-Dependent Apoptosis.Cancer research communications · 2024Article
- Met1-linked ubiquitination in cell signaling regulation.Biophysics reports · 2024Article
- Synthesis, antioxidant and antiZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway.Journal of inflammation research · 2024Article
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- Review
- Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO.Cellular & molecular biology letters · 2023Article
- Article
- Review
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that instigates several signaling cascades, including the NF-κB signaling pathway, to induce cell differentiation and proliferation. Overexpression and mutations of EGFR are found in up to 30% of solid tumors and correlate with a poor prognosis. Although it is known that EGFR-mediated NF-κB activation is involved in tumor development, the signaling axis is not well elucidated. Here, we found that plakophilin 2 (PKP2) and the linear ubiquitin chain assembly complex (LUBAC) were required for EGFR-mediated NF-κB activation. Upon EGF stimulation, EGFR recruited PKP2 to the plasma membrane, and PKP2 bridged HOIP, the catalytic E3 ubiquitin ligase in the LUBAC, to the EGFR complex. The recruitment activated the LUBAC complex and the linear ubiquitination of NEMO, leading to IκB phosphorylation and subsequent NF-κB activation. Furthermore, EGF-induced linear ubiquitination was critical for tumor cell proliferation and tumor development. Knockout of HOIP impaired EGF-induced NF-κB activity and reduced cell proliferation. HOIP knockout also abrogated the growth of A431 epidermal xenograft tumors in nude mice by more than 70%. More importantly, the HOIP inhibitor, HOIPIN-8, inhibited EGFR-mediated NF-κB activation and cell proliferation of A431, MCF-7, and MDA-MB-231 cancer cells. Overall, our study reveals a novel linear ubiquitination signaling axis of EGFR and that perturbation of HOIP E3 ubiquitin ligase activity is potential targeted cancer therapy.
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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.