ArticleMolecular and cellular biology2015
Substrate trapping proteomics reveals targets of the βTrCP2/FBXW11 ubiquitin ligase.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 73 citations in OpenAlex.
- A guide to mapping ubiquitin and ubiquitin-like E3 ligases to their substrates.The FEBS journal · 2026Review
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- Mechanistic Investigation of FBXW11-Mediated Ubiquitination and Degradation of HIC1 in Regulating IRF1 Transcription and Accelerating Acute Pancreatitis Progression.Digestive diseases and sciences · 2026Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis.The Journal of cell biology · 2025Article
- E3 ubiquitin ligase FBXW11-mediated downregulation of S100A11 promotes sensitivity to PARP inhibitor in ovarian cancer.Journal of pharmaceutical analysis · 2025Article
- A haploinsufficiency restoration strategy corrects neurobehavioral deficits in Nf1+/- mice.The Journal of clinical investigation · 2025Article
- A deficiency screen of the X chromosome for Rap1 GTPase dominant interacting genes in Drosophila border cell migration.G3 (Bethesda, Md.) · 2025Article
- Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities.Genome medicine · 2024Article
- SCFBiomedicines · 2024Article
- Building and breaking mechanical bridges between the nucleus and cytoskeleton: Regulation of LINC complex assembly and disassembly.Current opinion in cell biology · 2023Review
- A membrane-sensing mechanism links lipid metabolism to protein degradation at the nuclear envelope.The Journal of cell biology · 2023Article
- Intrathyroid thymic carcinoma: clinicopathological features and whole exome sequencing analysis.Virchows Archiv : an international journal of pathology · 2023Article
- Extracellular matrix stiffness regulates degradation of MST2 via SCFBiochimica et biophysica acta. General subjects · 2022Article
- Article
- Quality control mechanisms that protect nuclear envelope identity and function.The Journal of cell biology · 2022Review
- Global identification of phospho-dependent SCF substrates reveals a FBXO22 phosphodegron and an ERK-FBXO22-BAG3 axis in tumorigenesis.Cell death and differentiation · 2022Article
- FBXW11 contributes to stem-cell-like features and liver metastasis through regulating HIC1-mediated SIRT1 transcription in colorectal cancer.Cell death & disease · 2021Article
- Article
- SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration.Journal of cellular biochemistry · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Defining the full complement of substrates for each ubiquitin ligase remains an important challenge. Improvements in mass spectrometry instrumentation and computation and in protein biochemistry methods have resulted in several new methods for ubiquitin ligase substrate identification. Here we used the parallel adapter capture (PAC) proteomics approach to study βTrCP2/FBXW11, a substrate adaptor for the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase complex. The processivity of the ubiquitylation reaction necessitates transient physical interactions between FBXW11 and its substrates, thus making biochemical purification of FBXW11-bound substrates difficult. Using the PAC-based approach, we inhibited the proteasome to "trap" ubiquitylated substrates on the SCF(FBXW11) E3 complex. Comparative mass spectrometry analysis of immunopurified FBXW11 protein complexes before and after proteasome inhibition revealed 21 known and 23 putatively novel substrates. In focused studies, we found that SCF(FBXW11) bound, polyubiquitylated, and destabilized RAPGEF2, a guanine nucleotide exchange factor that activates the small GTPase RAP1. High RAPGEF2 protein levels promoted cell-cell fusion and, consequently, multinucleation. Surprisingly, this occurred independently of the guanine nucleotide exchange factor (GEF) catalytic activity and of the presence of RAP1. Our data establish new functions for RAPGEF2 that may contribute to aneuploidy in cancer. More broadly, this report supports the continued use of substrate trapping proteomics to comprehensively define targets for E3 ubiquitin ligases. All proteomic data are available via ProteomeXchange with identifier PXD001062.
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