ArticleProceedings of the National Academy of Sciences of the United States of America2018
Hsp70-Bag3 complex is a hub for proteotoxicity-induced signaling that controls protein aggregation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
- Microfluidics for protein interaction studies: current methods, challenges, and future perspectives.European biophysics journal : EBJ · 2026Review
- Structural insights into HRI kinase activity and inhibition.Biochemical Society transactions · 2026Review
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.Cell reports · 2026Article
- Autophagy activation via BAG3 gene therapy improves phenotype in a mouse model of LGMD1A.Molecular therapy. Advances · 2026Article
- Cell density-dependent nuclear-cytoplasmic shuttling of SETDB1 integrates with Hippo signaling to regulate YAP1-mediated transcription.FEBS letters · 2026Article
- An mTOR-Tfeb-Fabp7a Axis Ameliorates bag3 Cardiomyopathy via Decelerating Cardiac Aging.Aging cell · 2025Article
- Identification of a New Interesting BAG3 Modulator Able to Disrupt Cancer-Related Pathways.ChemMedChem · 2025Article
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.bioRxiv : the preprint server for biology · 2025Article
- Episodic transport of protein aggregates achieves a positive size selectivity in aggresome formation.Nature communications · 2025Article
- Cannabidiol and Alzheimer Disease: A Comprehensive Review and In Silico Insights Into Molecular Interactions.The European journal of neuroscience · 2025Review
- The BAG3-HSP70-CHIP axis controls the degradation of TGFBR2 in cardiac fibroblasts.Journal of molecular and cellular cardiology · 2025Article
- Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer's disease.Science advances · 2025Article
- Comparing In vitro Protein Aggregation Modelling Using Strategies Relevant to Neuropathologies.Cellular and molecular neurobiology · 2025Article
- Article
- G-CSF resistance of ELANE-mutant neutropenia depends on SERF1-containing truncated-neutrophil elastase aggregates.The Journal of clinical investigation · 2024Article
- CaMKII suppresses proteotoxicity by phosphorylating BAG3 in response to proteasomal dysfunction.EMBO reports · 2024Article
- A Cell-Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nonsense-mediated mRNA decay pathway in plants under stress: general gene regulatory mechanism and advances.Planta · 2024Review
- The NDR family of kinases: essential regulators of aging.Frontiers in molecular neuroscience · 2024Review
- Inhibition of SQSTM1 S403 phosphorylation facilitates the aggresome formation of ubiquitinated proteins during proteasome dysfunction.Cellular & molecular biology letters · 2023Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein abnormalities in cells are the cause of major pathologies, and a number of adaptive responses have evolved to relieve the toxicity of misfolded polypeptides. To trigger these responses, cells must detect the buildup of aberrant proteins which often associate with proteasome failure, but the sensing mechanism is poorly understood. Here we demonstrate that this mechanism involves the heat shock protein 70-Bcl-2-associated athanogene 3 (Hsp70-Bag3) complex, which upon proteasome suppression responds to the accumulation of defective ribosomal products, preferentially recognizing the stalled polypeptides. Components of the ribosome quality control system LTN1 and VCP and the ribosome-associated chaperone NAC are necessary for the interaction of these species with the Hsp70-Bag3 complex. This complex regulates important signaling pathways, including the Hippo pathway effectors LATS1/2 and the p38 and JNK stress kinases. Furthermore, under proteotoxic stress Hsp70-Bag3-LATS1/2 signaling regulates protein aggregation. We established that the regulated step was the emergence and growth of abnormal protein oligomers containing only a few molecules, indicating that aggregation is regulated at very early stages. The Hsp70-Bag3 complex therefore functions as an important signaling node that senses proteotoxicity and triggers multiple pathways that control cell physiology, including activation of protein aggregation.
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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.