ArticleGenes & development2015
FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 79 citations in OpenAlex.
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- Regulation of Autophagy by the Cdk1/p53/p21 Feedback Loop in an Interstitial Cystitis/Bladder Pain Syndrome Cell Model: Implications for Inflammatory Response.International urogynecology journal · 2025Article
- Role of Atg3, Atg5 and Atg12 in the crosstalk between apoptosis and autophagy in the posterior silk gland of Bombyx mori.Insect molecular biology · 2025Article
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- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
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- Ubiquitination Is a Novel Post-Translational Modification of VMP1 in Autophagy of Human Tumor Cells.International journal of molecular sciences · 2023Article
- Autophagy/Mitophagy Regulated by Ubiquitination: A Promising Pathway in Cancer Therapeutics.Cancers · 2023Review
- To Kill or to Be Killed: How Does the Battle between the UPS and Autophagy Maintain the Intracellular Homeostasis in Eukaryotes?International journal of molecular sciences · 2023Review
- Autosis as a selective type of cell death.Frontiers in cell and developmental biology · 2023Article
- Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases.Frontiers in immunology · 2023Review
- Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance.Cancer cell · 2022Article
- Degradation Mechanism of Autophagy-Related Proteins and Research Progress.International journal of molecular sciences · 2022Review
- Class III PI3K Biology.Current topics in microbiology and immunology · 2022Article
- A Seven-Autophagy-Related Long Non-Coding RNA Signature Can Accurately Predict the Prognosis of Patients with Renal Cell Carcinoma.International journal of general medicine · 2022Article
- LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13.Autophagy · 2021Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Vacuolar protein-sorting 34 (Vps34), the catalytic subunit in the class III PtdIns3 (phosphatidylinositol 3) kinase complexes, mediates the production of PtdIns3P, a key intracellular lipid involved in regulating autophagy and receptor degradation. However, the signal transduction pathways by which extracellular signals regulate Vps34 complexes and the downstream cellular mechanisms are not well understood. Here we show that DNA damage-activated mitotic arrest and CDK activation lead to the phosphorylation of Vps34, which provides a signal to promote its ubiquitination and proteasomal degradation mediated by FBXL20 (an F-box protein) and the associated Skp1 (S-phase kinase-associated protein-1)-Cullin1 complex, leading to inhibition of autophagy and receptor endocytosis. Furthermore, we show that the expression of FBXL20 is regulated by p53-dependent transcription. Our study provides a molecular pathway by which DNA damage regulates Vps34 complexes and its downstream mechanisms, including autophagy and receptor endocytosis, through SCF (Skp1-Cul1-F-box)-mediated ubiquitination and degradation. Since the expression of FBXL20 is regulated by p53-dependent transcription, the control of Vps34 ubiquitination and proteasomal degradation by FBXL20 and the associated SCF complex expression provides a novel checkpoint for p53 to regulate autophagy and receptor degradation in DNA damage response.
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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.