ArticleOncogene2014
BAG3 induction is required to mitigate proteotoxicity via selective autophagy following inhibition of constitutive protein degradation pathways.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.Cancers · 2023Review
- Article
- Reversible protein assemblies in the proteostasis network in health and disease.Frontiers in molecular biosciences · 2023Review
- Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.International journal of molecular sciences · 2022Review
- BAG family proteins contributes to autophagy-mediated multidrug resistance of tumor.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Linking α-synuclein-induced synaptopathy and neural network dysfunction in early Parkinson's disease.Brain communications · 2022Review
- Knockdown of Bcl-2-Associated Athanogene-3 Can Enhance the Efficacy of BGJ398 via Suppressing Migration and Inducing Apoptosis in Gastric Cancer.Digestive diseases and sciences · 2021Article
- Differential regulation of autophagy by STAU1 in alveolar rhabdomyosarcoma and non-transformed skeletal muscle cells.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Prognosis and Characterization of Immune Microenvironment in Acute Myeloid Leukemia Through Identification of an Autophagy-Related Signature.Frontiers in immunology · 2021Article
- Review
- A Crucial Role for the Protein Quality Control System in Motor Neuron Diseases.Frontiers in aging neuroscience · 2020Article
- BAG3 promotes autophagy and glutaminolysis via stabilizing glutaminase.Cell death & disease · 2019Article
- Lamin B is a target for selective nuclear PQC by BAG3: implication for nuclear envelopathies.Cell death & disease · 2019Article
- Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines.Food science & nutrition · 2018Article
- Compensatory increases of select proteostasis networks after Hsp70 inhibition in cancer cells.Journal of cell science · 2018Article
- Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age-dependent manner.Neurobiology of aging · 2018Article
- A BAG3 chaperone complex maintains cardiomyocyte function during proteotoxic stress.JCI insight · 2017Article
- The Role of the Heat Shock Protein B8 (HSPB8) in Motoneuron Diseases.Frontiers in molecular neuroscience · 2017Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simultaneous inhibition of the two major constitutive protein quality control (PQC) pathways, that is, the ubiquitin-proteasome system (UPS) and the aggresome-autophagy system, has been suggested as a promising strategy to trigger cell death in cancer cells. However, we observed that one third of rhabdomyosarcoma (RMS) cells survives parallel inhibition of the UPS by Bortezomib and the aggresome-autophagy pathway by the cytoplasmic histone deacetylase 6 inhibitor ST80, and is able to regrow upon drug removal, thus pointing to the induction of compensatory pathways. Here, we identify Bcl-2-associated athanogene 3 (BAG3) as a critical mediator of inducible resistance in surviving cells after concomitant blockage of constitutive PQC pathways by mitigating ST80/Bortezomib-triggered proteotoxicity via selective autophagy. ST80/Bortezomib cotreatment upregulates BAG3 mRNA and protein levels in surviving cells in addition to triggering the accumulation of insoluble protein aggregates. Intriguingly, knockdown of BAG3 by RNA interference severely impairs clearance of protein aggregates, significantly increases cell death and reduces long-term survival and clonogenic growth during recovery after ST80/Bortezomib cotreatment. Similarly, inhibition of autophagy by inducible autophagy-related protein 7 knockdown prevents removal of protein aggregates and cell regrowth during recovery after ST80/Bortezomib cotreatment. Also, the inhibition of lysosomal degradation using the V-ATPase pump inhibitor Bafilomycin A1 enhances accumulation of protein aggregates, and completely abolishes regrowth after Bortezomib/ST80-induced proteotoxic stress. By identifying BAG3 as a key mediator of inducible resistance by mitigating proteotoxicity via selective autophagy after inhibition of constitutive PQC systems, our study provides new insights into the regulation of PQC pathways in cancer cells and identifies new targets for therapeutic intervention.
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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.