ArticleNature cell biology2013
FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade.
Article in Nature cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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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.
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Who cites it
87 citing papers in PubMed, 123 citations in OpenAlex.
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- Protein tyrosine kinase-6 is post-translationally regulated by arginine methylation and ubiquitination.Cell death & disease · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- circSCAP-encoded SCAP-129aa mediates platinum resistance in triple-negative breast cancer via the PI3K/AKT pathway.Science China. Life sciences · 2026Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- Targeted inhibition of FBXL2 confers susceptibility of HER2-negative breast cancer to trastuzumab deruxtecan.Nature cancer · 2026Article
- HSP90AA1 restrains clear cell renal cell carcinoma progression by promoting CADM1 expression and suppressing the PI3K-AKT pathway through interaction with FBXO7.Cell death discovery · 2026Article
- The Role of the PI3K/Akt/mTOR Pathway in Atherosclerosis: Mechanisms, Therapeutic Potential, and Emerging Targeted Treatments.Current atherosclerosis reports · 2025Review
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- Ubiquitin proteasome system in cardiac fibrosis.Journal of advanced research · 2025Review
- PIK3R2 immunostaining status predicts prognosis in patients with newly diagnosed glioblastoma treated with an autologous tumor vaccine.Journal of neuro-oncology · 2025Article
- Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.Immune network · 2025Review
- Exploring the molecular mechanism of Xiao Ji (Asian biomedicine : research, reviews and news · 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
- Identification of macrophage polarisation and mitochondria-related biomarkers in diabetic retinopathy.Journal of translational medicine · 2025Article
- PPTC7 antagonizes mitophagy by promoting BNIP3 and NIX degradation via SCFEMBO reports · 2024Article
- The emerging and diverse roles of F-box proteins in spermatogenesis and male infertility.Cell regeneration (London, England) · 2024Review
- Review
- Distinctive genes and signaling pathways associated with type 2 diabetes-related periodontitis: Preliminary study.PloS one · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
F-box proteins are the substrate-recognition subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes. Purification of the F-box protein FBXL2 identified the PI(3)K regulatory subunit p85β and tyrosine phosphatase PTPL1 as interacting proteins. FBXL2 interacts with the pool of p85β that is free of p110 PI(3)K catalytic subunits and targets this pool for ubiquitylation and subsequent proteasomal degradation. FBXL2-mediated degradation of p85β is dependent on the integrity of its CaaX motif. Whereas most SCF substrates require phosphorylation to interact with their F-box proteins, phosphorylation of p85β on Tyr 655, which is adjacent to the degron, inhibits p85β binding to FBXL2. Dephosphorylation of phospho-Tyr-655 by PTPL1 stimulates p85β binding to and degradation through FBXL2. Finally, defects in the FBXL2-mediated degradation of p85β inhibit the binding of p110 subunits to IRS1, attenuate the PI(3)K signalling cascade and promote autophagy. We propose that FBXL2 and PTPL1 suppress p85β levels, preventing the inhibition of PI(3)K by an excess of free p85 that could compete with p85-p110 heterodimers for IRS1.
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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.