ArticleCell death and differentiation2018
β-Trcp ubiquitin ligase and RSK2 kinase-mediated degradation of FOXN2 promotes tumorigenesis and radioresistance in lung cancer.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Ubiquitin signaling in tumor-associated macrophage reprogramming: mechanisms and therapeutic opportunities in cancers.Biomarker research · 2026Review
- Cigarette smoking combines with genetic variants to regulate FOXN3 and associate with bladder cancer risk.Archives of toxicology · 2026Article
- Binding domain mutations provide insight into CTCF's relationship with chromatin and its contribution to gene regulation.Cell genomics · 2025Article
- Brain and cancer associated binding domain mutations provide insight into CTCF's relationship with chromatin and its ability to act as a chromatin organizer.Research square · 2024Article
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- The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.Biomedicines · 2023Review
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- Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity.Journal of cancer research and clinical oncology · 2023Review
- ZNRF2 as an oncogene is transcriptionally regulated by CREB1 in breast cancer models.Human cell · 2023Article
- MicroRNA-188-5p inhibits hepatocellular carcinoma proliferation and migration by targeting forkhead box N2.BMC cancer · 2023Article
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- A novel ribosomal protein S6 kinase 2 inhibitor attenuates the malignant phenotype of cutaneous malignant melanoma cells by inducing cell cycle arrest and apoptosis.Bioengineered · 2022Article
- Regulation of retinal amacrine cell generation by miR-216b and Foxn3.Development (Cambridge, England) · 2022Article
- RSK2 promotes melanoma cell proliferation and vemurafenib resistanceFrontiers in pharmacology · 2022Article
- HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2.International journal of molecular sciences · 2021Article
- Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma.Cancers · 2021Article
- Tracing the evolution of aneuploid cancers by multiregional sequencing with CRUST.Briefings in bioinformatics · 2021Article
- Dysregulation of the Ubiquitin Proteasome System in Human Malignancies: A Window for Therapeutic Intervention.Cancers · 2021Review
- Article
- Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant expression of FOXN2, a member of the Forkhead box transcription factors, has been found in several types of cancer. However, the underlying mechanisms of FOXN2 deregulation in tumorigenesis remain largely unknown. Here, we find that FOXN2 binds to and is ubiquitinated by β-Trcp ubiquitin ligase and RSK2 kinase for degradation. Furthermore, we demonstrate that the Ser365 and Ser369 sites in a conserved DSGYAS motif are critical for the degradation of FOXN2 by β-Trcp and RSK2. Moreover, gain-of-function and loss-of-function studies show that FOXN2 impairs cell proliferation in vitro and in vivo and enhances the radiosensitivity of lung cancer. Importantly, β-Trcp-mediated and RSK2-mediated degradation of FOXN2 promotes tumorigenesis and radioresistance in lung cancer cells. Collectively, our study reveals a novel post-translational modification of FOXN2 and suggests that FOXN2 may be a potential therapeutic and radiosensitization target for lung cancer.
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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.