ArticleMolecular & cellular proteomics : MCP2015
Proteomic analysis reveals a role for Bcl2-associated athanogene 3 and major vault protein in resistance to apoptosis in senescent cells by regulating ERK1/2 activation.
Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- FAK signaling pathways are modulated by HSPB8 and BAG3 in breast cancer.Cell communication and signaling : CCS · 2026Article
- Vault Particles in Cancer Progression, Multidrug Resistance, and Drug Delivery: Current Insights and Future Applications.International journal of molecular sciences · 2025Review
- Single-cell RNA sequencing to detect age-associated genes that identify senescent cells in the liver of aged mice.Scientific reports · 2023Article
- A genetically encoded photoproximity labeling approach for mapping protein territories.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.International journal of molecular sciences · 2022Review
- Small but Powerful: The Human Vault RNAs as Multifaceted Modulators of Pro-Survival Characteristics and Tumorigenesis.Cancers · 2022Review
- The role of BAG3 in health and disease: A "Magic BAG of Tricks".Journal of cellular biochemistry · 2022Review
- The Proteomics and Metabolomics Analysis for Screening the Molecular Targets of Action of β-Eudesmol in Cholangiocarcinoma.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Review
- Review
- BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction pathways in triple negative breast cancer.Oncotarget · 2018Article
- Targeting the PI3K/Akt/mTOR signalling pathway in Cystic Fibrosis.Scientific reports · 2017Article
- The Role of the Multifunctional BAG3 Protein in Cellular Protein Quality Control and in Disease.Frontiers in molecular neuroscience · 2017Review
- ERK-mediated phosphorylation of BIS regulates nuclear translocation of HSF1 under oxidative stress.Experimental & molecular medicine · 2016Article
- Article
- Dissecting cellular senescence and SASP inInflammation and regeneration · 2016Review
- Role of lncRNAs in Cellular Aging.Frontiers in endocrinology · 2016Review
- Cellular senescence in aging and age-related disease: from mechanisms to therapy.Nature medicine · 2015Review
- Estrogen receptor α regulates non-canonical autophagy that provides stress resistance to neuroblastoma and breast cancer cells and involves BAG3 function.Cell death & disease · 2015Article
- Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Senescence is a prominent solid tumor response to therapy in which cells avoid apoptosis and instead enter into prolonged cell cycle arrest. We applied a quantitative proteomics screen to identify signals that lead to therapy-induced senescence and discovered that Bcl2-associated athanogene 3 (Bag3) is up-regulated after adriamycin treatment in MCF7 cells. Bag3 is a member of the BAG family of co-chaperones that interacts with Hsp70. Bag3 also regulates major cell-signaling pathways. Mass spectrometry analysis of the Bag3 Complex revealed a novel interaction between Bag3 and Major Vault Protein (MVP). Silencing of Bag3 or MVP shifts the cellular response to adriamycin to favor apoptosis. We demonstrate that Bag3 and MVP contribute to apoptosis resistance in therapy-induced senescence by increasing the level of activation of extracellular signal-regulated kinase1/2 (ERK1/2). Silencing of either Bag3 or MVP decreased ERK1/2 activation and promoted apoptosis in adriamycin-treated cells. An increase in nuclear accumulation of MVP is observed during therapy-induced senescence and the shift in MVP subcellular localization is Bag3-dependent. We propose a model in which Bag3 binds to MVP and facilitates MVP accumulation in the nucleus, which sustains ERK1/2 activation. We confirmed that silencing of Bag3 or MVP shifts the response toward apoptosis and regulates ERK1/2 activation in a panel of diverse breast cancer cell lines. This study highlights Bag3-MVP as an important complex that regulates a potent prosurvival signaling pathway and contributes to chemotherapy resistance in breast cancer.
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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.