ArticleThe Journal of biological chemistry2014
F-box only protein 31 (FBXO31) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Research advancements regarding the relationship between FBXO2 and malignant tumors (Review).Molecular medicine reports · 2025Review
- Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.Molecular biomedicine · 2025Article
- Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone.Biomolecules · 2025Review
- FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy.Nature communications · 2025Article
- SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Aberrantly High FBXO31 Impairs Oocyte Quality in Premature Ovarian Insufficiency.Aging and disease · 2024Article
- Inhibitors Targeting the F-BOX Proteins.Cell biochemistry and biophysics · 2023Review
- Natural Compounds: Potential Therapeutics for the Inhibition of Cartilage Matrix Degradation in Osteoarthritis.Life (Basel, Switzerland) · 2022Review
- p38MAPK Signaling Pathway in Osteoarthritis: Pathological and Therapeutic Aspects.Journal of inflammation research · 2022Review
- Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade.International journal of biological sciences · 2022Article
- Roles of microRNAs in tumorigenesis and metastasis of esophageal squamous cell carcinoma.World journal of clinical oncology · 2021Review
- Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells.International journal of molecular sciences · 2021Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- The role of E3 ubiquitin ligases in the development and progression of glioblastoma.Cell death and differentiation · 2021Review
- Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer.Theranostics · 2021Article
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
- MicroRNA-338-5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id-1.Cancer science · 2019Article
- Ethyl pyruvate inhibits LPS induced IPEC-J2 inflammation and apoptosis through p38 and ERK1/2 pathways.Cell cycle (Georgetown, Tex.) · 2019Article
- Genome-wide association study of an unusual dolphin mortality event reveals candidate genes for susceptibility and resistance to cetacean morbillivirus.Evolutionary applications · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p38 MAPK signal transduction pathway plays an important role in inflammatory and stress responses. MAPKK6 (MKK6), a dual specificity protein kinase, is a p38 activator. Activation of the MKK6-p38 pathway is kept in check by multiple layers of regulations, including autoinhibition, dimerization, scaffold proteins, and Lys-63-linked polyubiquitination. However, the mechanisms underlying deactivation of MKK6-p38, which is crucial for maintaining the magnitude and duration of signal transduction, are not well understood. Lys-48-linked ubiquitination, which marks substrates for proteasomal degradation, is an important negative posttranslational regulatory machinery for signal pathway transduction. Here we report that the accumulation of F-box only protein 31 (FBXO31), a component of Skp1 · Cul1 · F-box protein E3 ligase, negatively regulated p38 activation in cancer cells upon genotoxic stresses. Our results show that FBXO31 binds to MKK6 and mediates its Lys-48-linked polyubiquitination and degradation, thereby functioning as a negative regulator of MKK6-p38 signaling and protecting cells from stress-induced cell apoptosis. Taken together, our findings uncover a new mechanism of deactivation of MKK6-p38 and substantiate a novel regulatory role of FBXO31 in stress response.
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