ArticleAutophagy2024
VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- Organelle contact reorganization drives calcium-dependent autophagy under proteostatic stress.Autophagy · 2026Article
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- Discovery and Characterization of Inhibitors of Ubiquitin-Like Modifier Activating Enzyme 5 (UBA5): Targeting the UFMylation Pathway in Cancer and Neurodegenerative Diseases.ACS chemical biology · 2026Article
- Piroctone olamine promotes BECN1 transcription and activates autophagy by targeting HDAC6 in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Exploring the potential involvement of UFSP2 in spindle assembly checkpoint regulation in breast cancer.Molecular biology reports · 2026Article
- The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Optimization of protein UFMylation modification method and its application in substrate identification in human cells.The Journal of biological chemistry · 2026Article
- K48 and K63 linkage-competed ubiquitination of BECN1 promotes circPDE4D-mediated autophagy in chronic obstructive pulmonary disease.Cell death & disease · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- SVIP in plasma: a candidate blood-based biomarker for early detection of amnestic mild cognitive impairment.Frontiers in aging neuroscience · 2026Article
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Unveiling the hidden regulators: how post-translational modifications influence the progression and treatment of hepatocellular carcinoma.Frontiers in oncology · 2026Review
- SQSTM1/p62 UFMylation Enhances Autophagic Clearance of Pathogenic Mutant Huntingtin.International journal of biological sciences · 2026Article
- Targeting VCP enhances colorectal cancer therapy through STING stabilization.Journal for immunotherapy of cancer · 2025Article
- tRNA-derived fragment tRF-24 drives CELF1 phase separation to promote oncogenic splicing in esophageal squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- Akt-phosphorylated UFL1 UFMylates ArpC4 to promote metastasis.Nature structural & molecular biology · 2025Article
- Knockdown of MIR205HG prevents cell proliferation, migration and invasion through autophagy and ferroptosis pathways in lung adenocarcinoma.Translational cancer research · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
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Authors and funding
7 authors.
Funding
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Abstract
Macroautophagy/autophagy is essential for the degradation and recycling of cytoplasmic materials. The initiation of this process is determined by phosphatidylinositol-3-kinase (PtdIns3K) complex, which is regulated by factor BECN1 (beclin 1). UFMylation is a novel ubiquitin-like modification that has been demonstrated to modulate several cellular activities. However, the role of UFMylation in regulating autophagy has not been fully elucidated. Here, we found that VCP/p97 is UFMylated on K109 by the E3 UFL1 (UFM1 specific ligase 1) and this modification promotes BECN1 stabilization and assembly of the PtdIns3K complex, suggesting a role for VCP/p97 UFMylation in autophagy initiation. Mechanistically, VCP/p97 UFMylation stabilizes BECN1 through ATXN3 (ataxin 3)-mediated deubiquitination. As a key component of the PtdIns3K complex, stabilized BECN1 facilitates assembly of this complex. Re-expression of VCP/p97, but not the UFMylation-defective mutant, rescued the VCP/p97 depletion-induced increase in MAP1LC3B/LC3B protein expression. We also showed that several pathogenic VCP/p97 mutations identified in a variety of neurological disorders and cancers were associated with reduced UFMylation, thus implicating VCP/p97 UFMylation as a potential therapeutic target for these diseases.
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