ArticleInternational journal of molecular sciences2022
Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- FBXW7α regulates amyloid pathology by mediating ubiquitination and degradation of BACE1 in Alzheimer's disease.Cell death discovery · 2026Article
- Genetic Variants from Large Cohorts and Familial Studies Implicate Common Mechanisms in Schizophrenia.Biology · 2026Review
- ERK inhibits Capicua repressor function via multisite phosphorylation.Journal of cell science · 2026Article
- Class IIa HDACs forced degradation allows resensitization of oxaliplatin-resistant FBXW7-mutated colorectal cancer.Molecular oncology · 2026Article
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- Sorafenib promotes the E3 ubiquitin ligase FBXW7 to increase tau degradation and ameliorate tauopathies.Acta pharmaceutica Sinica. B · 2025Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- Editorial for the Special Issue "MAPK in Health and Disease".International journal of molecular sciences · 2024Article
- Epidermal growth factor receptor (EGFR) is a target of the tumor-suppressor E3 ligase FBXW7.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies.Cell death & disease · 2024Review
- Chromatin Ubiquitination Guides DNA Double Strand Break Signaling and Repair.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A FBXW7 is an F-box E3 ubiquitin-ligase affecting cell growth by controlling protein degradation. Mechanistically, its effect on its substrates depends on the phosphorylation of degron motifs, but the abundance of these phosphodegrons has not been systematically explored. We used a ratiometric protein degradation assay geared towards the identification of FBXW7-binding degron motifs phosphorylated by mitogen-activated protein kinases (MAPKs). Most of the known FBXW7 targets are localized in the nucleus and function as transcription factors. Here, in addition to more transcription affecting factors (ETV5, KLF4, SP5, JAZF1, and ZMIZ1 CAMTA2), we identified phosphodegrons located in proteins involved in chromatin regulation (ARID4B, KMT2E, KMT2D, and KAT6B) or cytoskeletal regulation (MAP2, Myozenin-2, SMTL2, and AKAP11), and some other proteins with miscellaneous functions (EIF4G3, CDT1, and CCAR2). We show that the protein level of full-length ARID4B, ETV5, JAZF1, and ZMIZ1 are affected by different MAPKs since their FBXW7-mediated degradation was diminished in the presence of MAPK-specific inhibitors. Our results suggest that MAPK and FBXW7 partnership plays an important cellular role by directly affecting the level of key regulatory proteins. The data also suggest that the p38α-controlled phosphodegron in JAZF1 may be responsible for the pathological regulation of the cancer-related JAZF1-SUZ12 fusion construct implicated in endometrial stromal sarcoma.
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Registered trials
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.