ArticleAutophagy2015
Chaperone-mediated autophagy prevents apoptosis by degrading BBC3/PUMA.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Dietary Modulation of CMA: Implications for Cancer Prevention and Therapy.Physiology (Bethesda, Md.) · 2027Review
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- Glucocorticoid Receptor Signaling in Myeloid Cells Orchestrates Inflammation Resolution and Muscle Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ZDHHC8-mediated S-palmitoylation of RAD21 causes mitochondrial dysfunction in diabetic nephropathy via inhibiting ACSM3 transcription.Cell death and differentiation · 2026Article
- Chaperone-mediated autophagy as a regulator of hallmarks of cancer.Frontiers in oncology · 2026Review
- NONO modulates tumorigenesis and metastatic potential of lung squamous cell carcinoma.Frontiers in oncology · 2026Article
- Targeting SERPINB3-MAPK axis-mediated cuproptosis resistance enhances the response to antitumor immunotherapy.Molecular cancer · 2025Article
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Aging-related signature stratifies LUAD prognosis and uncovers senescence-induced chemoresistance via NF-κB/RELA activation.Respiratory research · 2025Article
- Chaperone-mediated autophagy directs a dual mechanism to balance premature senescence and senolysis to prevent intervertebral disc degeneration.Bone research · 2025Article
- Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways.Cancer cell international · 2025Article
- The c.119-123dup5bp mutation in human γC-crystallin destabilizes the protein and activates the unfolded protein response to cause highly variable cataracts.Scientific reports · 2025Article
- Multiple regulatory mechanisms, functions and therapeutic potential of chaperone-mediated autophagy.Theranostics · 2025Review
- Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).Molecular medicine reports · 2025Review
- Prognostic genes related to mitochondrial dynamics and mitophagy in diffuse large B-cell lymphoma are identified and validated using an integrated analysis of bulk and single-cell RNA sequencing.Frontiers in immunology · 2025Article
- The novelAutophagy · 2024Article
- Autophagy in Disease Onset and Progression.Aging and disease · 2024Review
- LAMP2A regulates cisplatin resistance in colorectal cancer through mediating autophagy.Journal of cancer research and clinical oncology · 2024Article
- LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles.Autophagy · 2023Review
- Chaperone-mediated autophagy: Molecular mechanisms, biological functions, and diseases.MedComm · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a potentially inimical pathway and together with apoptosis, may be activated by similar stress stimuli that can lead to cell death. The molecular cues that dictate the cell fate choice between autophagy and apoptosis remain largely unknown. Here we report that the proapoptotic protein BBC3/PUMA (BCL2 binding component 3) is a bona fide substrate of chaperone-mediated autophagy (CMA). BBC3 associates with HSPA8/HSC70 (heat shock 70kDa protein 8), leading to its lysosome translocation and uptake. Inhibition of CMA results in stabilization of BBC3, which in turn sensitizes tumor cells to undergo apoptosis. We further demonstrate that upon TNF (tumor necrosis factor) treatment, IKBKB/IKKβ (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase β)-mediated BBC3 Ser10 phosphorylation is crucial for BBC3 stabilization via blocking its degradation by CMA. Mechanistically, Ser10 phosphorylation facilitates BBC3 translocation from the cytosol to mitochondria. BBC3 stabilization resulting from either Ser10 phosphorylation or CMA inhibition potentiates TNF-induced apoptotic cell death. Our findings thus reveal that the selective degradation of BBC3 underlies the prosurvival role of CMA and define a previously unappreciated proapoptotic role of IKBKB that acts through phosphorylation-mediated stabilization of BBC3, thereby promoting TNF-triggered apoptosis.
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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.