ArticleExperimental & molecular medicine2022
FBXW7-mediated ERK3 degradation regulates the proliferation of lung cancer cells.
Article in Experimental & molecular medicine, 2022. 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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17 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting MAPK Pathways in Skin, Thyroid, and Pancreatic Cancer: A Perspective on Synthetic Inhibitors and Natural Modulators.Advanced biology · 2026Review
- Juglone induces GSDME axis pyroptosis in osteosarcoma cells via the JNK/P38 MAPK pathway.Scientific reports · 2026Article
- FBXW7 regulates MAP7 through ubiquitination to affect the phenotypic characteristics and paclitaxel sensitivity of paclitaxel-resistant lung adenocarcinoma cells.European journal of medical research · 2025Article
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- Cancer-associated mesenchymal stem cell exosomes facilitate non-small cell lung cancer cell viability and invasiveness by delivering miR-182 in a FBXW7-related AKT and ERK-dependent pathway.Oncology letters · 2025Article
- Atypical MAPKs in cancer.The FEBS journal · 2025Review
- Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation.Clinical and translational medicine · 2025Article
- Identification of novel therapeutic targets for head and neck squamous cell carcinoma through bioinformatics analysis.Scientific reports · 2024Article
- SPOP-mediated RIPK3 destabilization desensitizes LPS/sMAC/zVAD-induced necroptotic cell death.Cellular and molecular life sciences : CMLS · 2024Article
- CREG1 attenuates doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis of cardiomyocytes.Redox biology · 2024Article
- CALU promotes lung adenocarcinoma progression by enhancing cell proliferation, migration and invasion.Respiratory research · 2024Article
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- Review
- Impact of KRAS mutation on the tumor microenvironment in colorectal cancer.International journal of biological sciences · 2024Review
- Transcriptomics Provides Novel Insights into the Regulatory Mechanism of IncRNA HIF1 A-AS1 on Vascular Smooth Muscle Cells.Brazilian journal of cardiovascular surgery · 2023Article
- Genome-wide analysis of WD40 protein family and functional characterization ofFrontiers in plant science · 2023Article
- ERK3 and DGKζ interact to modulate cell motility in lung cancer cells.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family, members of which play essential roles in diverse cellular processes during carcinogenesis, including cell proliferation, differentiation, migration, and invasion. Unlike other MAPKs, ERK3 is an unstable protein with a short half-life. Although deubiquitination of ERK3 has been suggested to regulate the activity, its ubiquitination has not been described in the literature. Here, we report that FBXW7 (F-box and WD repeat domain-containing 7) acts as a ubiquitination E3 ligase for ERK3. Mammalian two-hybrid assay and immunoprecipitation results demonstrated that ERK3 is a novel binding partner of FBXW7. Furthermore, complex formation between ERK3 and the S-phase kinase-associated protein 1 (SKP1)-cullin 1-F-box protein (SCF) E3 ligase resulted in the destabilization of ERK3 via a ubiquitination-mediated proteasomal degradation pathway, and FBXW7 depletion restored ERK3 protein levels by inhibiting this ubiquitination. The interaction between ERK3 and FBXW7 was driven by binding between the C34D of ERK3, especially at Thr417 and Thr421, and the WD40 domain of FBXW7. A double mutant of ERK3 (Thr417 and Thr421 to alanine) abrogated FBXW7-mediated ubiquitination. Importantly, ERK3 knockdown inhibited the proliferation of lung cancer cells by regulating the G
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