ArticleCell reports2012
SCF(Fbw7) modulates the NFkB signaling pathway by targeting NFkB2 for ubiquitination and destruction.
Article in Cell reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- The role of the WD40-repeat protein family in cancer.Molecular cancer · 2026Review
- Dynamic modulation of the non-canonical NF-κB signaling pathway for HIV shock and kill.Frontiers in cellular and infection microbiology · 2024Review
- Functional analysis reveals driver cooperativity and novel mechanisms in endometrial carcinogenesis.EMBO molecular medicine · 2023Article
- FBXW7 in breast cancer: mechanism of action and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2023Review
- Chicken Glycogen Synthase Kinase 3β Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells.Microbiology spectrum · 2023Article
- FBXW7β isoform drives transcriptional activation of the proinflammatory TNF cluster in human pro-B cells.Blood advances · 2023Article
- Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases.Frontiers in immunology · 2023Review
- Hepatic neddylation deficiency triggers fatal liver injury via inducing NF-κB-inducing kinase in mice.Nature communications · 2022Article
- Comprehensive Study of Human FBXW7 Deleterious nsSNP's Functional Inference and Susceptibility to Gynaecological Cancer.Applied biochemistry and biotechnology · 2022Article
- Dysregulation of FBW7 in malignant lymphoproliferative disorders.Frontiers in oncology · 2022Review
- E3 ubiquitin ligases in the acute leukemic signaling pathways.Frontiers in physiology · 2022Review
- Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses.Cell discovery · 2021Review
- Review
- Tumor Suppressor FBXW7 and Its Regulation of DNA Damage Response and Repair.Frontiers in cell and developmental biology · 2021Review
- Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites.Frontiers in immunology · 2021Review
- Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study.Signal transduction and targeted therapy · 2020Review
- The Negative Cross-Talk between SAG/RBX2/ROC2 and APC/C E3 Ligases in Regulation of Cell Cycle Progression and Drug Resistance.Cell reports · 2020Article
- E3 Ubiquitin Ligase Fbw7 Regulates the Survival of Mature B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- miRNA-129/FBW7/NF-κB, a Novel Regulatory Pathway in Inflammatory Bowel Disease.Molecular therapy. Nucleic acids · 2020Article
- FBW7 in hematological tumors.Oncology letters · 2020Review
Corrections and comments
- Erratum issuedSCF2025
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The NFkB/Rel family of proteins play critical roles in a variety of cellular processes. Thus, their physiological activation is tightly controlled. Recently, the NFkB2/p100 precursor has been characterized as the fourth IkB type of suppressor for NFkB. However, the molecular mechanism(s) underlying regulated destruction of NFkB2 remains largely unknown. Here, we report that, unlike other IkBs, ubiquitination and destruction of NFkB2 are governed by SCF(Fbw7) in a GSK3-dependent manner. In Fbw(7-/-) cells, elevated expression of NFkB2/p100 leads to a subsequent reduction in NFkB signaling pathways and elevated sensitivity to TNFa-induced cell death. Reintroducing wild-type Fbw7, but not disease-derived mutant forms of Fbw7, rescues NFkB activity. Furthermore, T cell-specific depletion of Fbw7 also leads to reduced NFkB activity and perturbed T cell differentiation. Therefore, our work identifies Fbw7 as a physiological E3 ligase controlling NFkB20s stability. It further implicates that Fbw7 might exert its tumor-suppressor function by regulating NFkB activity.
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What OpenQuestion holds
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.