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Cited by 133Heat shock proteins researchCell death mechanisms and regulationUbiquitin and proteasome pathways

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Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells

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Götz, Rudolf, Wiese, Stefan, Takayama, Shinichi, Camarero, Guadalupe C, Rossoll, Wilfried, Schweizer, Ulrich, Troppmair, Jakob, Jablonka, Sibylle, Holtmann, Bettina, Reed, John C, Rapp, Ulf R, Sendtner, Michael·2005·Nature Neuroscience
DOI 10.1038/nn1524PMC PMC1361767
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Abstract

Bag1 is a cochaperone for the heat-shock protein Hsp70 that interacts with C-Raf, B-Raf, Akt, Bcl-2, steroid hormone receptors and other proteins. Here we use targeted gene disruption in mice to show that Bag1 has an essential role in the survival of differentiating neurons and hematopoietic cells. Cells of the fetal liver and developing nervous system in Bag1-/- mice underwent massive apoptosis. Lack of Bag1 did not disturb the primary function of Akt or Raf, as phosphorylation of the forkhead transcription factor FKHR and activation of extracellular signal-regulated kinase (Erk)-1/2 were not affected. However, the defect was associated with the disturbance of a tripartite complex formed by Akt, B-Raf and Bag1, in addition to the absence of Bad phosphorylation at Ser136. We also observed reduced expression of members of the inhibitor of apoptosis (IAP) family. Our data show that Bag1 is a physiological mediator of extracellular survival signals linked to the cellular mechanisms that prevent apoptosis in hematopoietic and neuronal progenitor cells.

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  • BAG-1 interacts with Hsp70 family of molecular chaperones, displaying cytoprotective activities and effects on signal transduction and transcription, suggesting a function in overcoming cellular stress and inflammation.

    “BAG-1 is known to interact with heat shock protein 70 (Hsp70) family of molecular chaperones, displaying a variety of cytoprotective activities and effects on signal transduction and transcription, suggesting a function in overcoming cellular stress and inflammation38,39.”

    From TNF-alpha-induced microglia activation requires miR-342: Impact on NF-kB signaling and neurotoxicity (2020) · cites this paper as [38]

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Research works printed but not linked: 40

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Metadata

Authors
Götz, R., Wiese, S., Takayama, S., Camarero, G. C., Rossoll, W., Schweizer, U., Troppmair, J., Jablonka, S., Holtmann, B., Reed, J. C., Rapp, U. R., & Sendtner, M.
Affiliations
  • University of Würzburg (DE)
  • Innsbruck Medical University (AT)
  • Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author
Sendtner, Michael
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2005-08-21
Volume
8
Issue
9
Pages
1169-1178
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn1524
PMC
PMC1361767
OpenAlex
W2084481001
Cited by
133
References
0
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 6
FWCI
4.44
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • National Cancer Institute (CA67385, R01CA067329)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
BAG-1, Hsp70 co-chaperone, apoptosis, hematopoietic cells, neuronal differentiation, neuronal survival, Akt, BRAF, Bad phosphorylation, inhibitor of apoptosis proteins, FOXO1, ERK1/2, cell survival signaling
MeSH terms
PAX6 Transcription Factor, Alkaline Phosphatase, Analysis of Variance, Animals, Carrier Proteins, Cell Count, Cell Differentiation, Cell Survival, Cells, Cultured, Electron Transport Complex IV, DNA-Binding Proteins, Embryo, Mammalian, Eye Proteins, Fibroblasts, Hematopoietic Stem Cells, Immunohistochemistry, Intermediate Filament Proteins, Isoenzymes, Liver, Membrane Proteins, Motor Neurons, Mutation, Nerve Tissue Proteins, Propidium, Proto-Oncogene Proteins, Repressor Proteins, RNA, Messenger, Spinal Cord, Transcription Factors, Transfection, Blotting, Southern, Blotting, Western, Neurofilament Proteins, Protein Serine-Threonine Kinases, Mice, Knockout, Homeodomain Proteins, HSP70 Heat-Shock Proteins, Reverse Transcriptase Polymerase Chain Reaction, In Situ Nick-End Labeling, RNA, Small Interfering, Immunoprecipitation, Proto-Oncogene Proteins B-raf, bcl-Associated Death Protein, Proto-Oncogene Proteins c-akt, Mice, Rats, Paired Box Transcription Factors, Nestin

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