ArticleProceedings of the National Academy of Sciences of the United States of America2015
F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 63 citations in OpenAlex.
- USP21 functions as an oncogenic regulator of the Mdm2-p53 axis in colorectal cancer.Cell death discovery · 2026Article
- Harnessing FBXO31 with Terminal Amide-Functionalized Molecules for Targeted Protein Degradation.Journal of the American Chemical Society · 2026Article
- Poxvirus infection triggers remodeling of host m⁶A epitranscriptome and benefits from the m⁶A regulatory responses.Virology journal · 2026Article
- FBXO31-induced ABL2 ubiquitination increases cystine-glutamate antiporter-mediated ferroptosis and inhibits malignant progression in triple-negative breast cancer.American journal of translational research · 2026Article
- Research advancements regarding the relationship between FBXO2 and malignant tumors (Review).Molecular medicine reports · 2025Review
- Limited cell-autonomous anticancer mechanisms in long-lived bats.Nature communications · 2025Article
- FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy.Nature communications · 2025Article
- Aberrantly High FBXO31 Impairs Oocyte Quality in Premature Ovarian Insufficiency.Aging and disease · 2024Article
- FBXO31 is upregulated by METTL3 to promote pancreatic cancer progression via regulating SIRT2 ubiquitination and degradation.Cell death & disease · 2024Article
- Article
- Apolipoprotein C3-Rich Low-Density Lipoprotein Induces Endothelial Cell Senescence via FBXO31 and Its Inhibition by Sesamol In Vitro and In Vivo.Biomedicines · 2022Article
- Extracellular circulating miRNAs as stress-related signature to search and rescue dogs.Scientific reports · 2022Article
- Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis.Cell reports · 2021Article
- Proteasomal Regulation of Mammalian SPT16 in Controlling Transcription.Molecular and cellular biology · 2021Article
- Ubiquitin-specific protease 53 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.Cell death & disease · 2021Article
- Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.Acta pharmaceutica Sinica. B · 2021Review
- APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis.Seminars in cancer biology · 2020Review
- Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain.Nature communications · 2020Article
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
- MDM2-P53 Signaling Pathway-Mediated Upregulation of CDC20 Promotes Progression of Human Diffuse Large B-Cell Lymphoma.OncoTargets and therapy · 2020Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The tumor suppressor p53 plays a critical role in maintaining genomic stability. In response to genotoxic stress, p53 levels increase and induce cell-cycle arrest, senescence, or apoptosis, thereby preventing replication of damaged DNA. In unstressed cells, p53 is maintained at a low level. The major negative regulator of p53 is MDM2, an E3 ubiquitin ligase that directly interacts with p53 and promotes its polyubiquitination, leading to the subsequent destruction of p53 by the 26S proteasome. Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 stability. Because of the important role of MDM2 in modulating p53 function, it is critical to understand how MDM2 levels are regulated. Here we show that the F-box protein FBXO31, a candidate tumor suppressor encoded in 16q24.3 for which there is loss of heterozygosity in various solid tumors, is responsible for promoting MDM2 degradation. Following genotoxic stress, FBXO31 is phosphorylated by the DNA damage serine/threonine kinase ATM, resulting in increased levels of FBXO31. FBXO31 then interacts with and directs the degradation of MDM2, which is dependent on phosphorylation of MDM2 by ATM. FBXO31-mediated loss of MDM2 leads to elevated levels of p53, resulting in growth arrest. In cells depleted of FBXO31, MDM2 is not degraded and p53 levels do not increase following genotoxic stress. Thus, FBXO31 is essential for the classic robust increase in p53 levels following DNA damage.
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