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

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....

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Veröffentlicht in:	Nature neuroscience Jg. 8; H. 9; S. 1169 - 1178
Hauptverfasser:	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
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.09.2005 Nature Publishing Group
Schlagworte:	Alkaline Phosphatase - metabolism Analysis of Variance Animal Genetics and Genomics Animals bcl-Associated Death Protein Behavioral Sciences Binding proteins Biological Techniques Biomedical and Life Sciences Biomedicine Blotting, Southern - methods Blotting, Western - methods Carrier Proteins - metabolism Cell Count - methods Cell Differentiation - physiology Cell Survival - physiology Cells, Cultured DNA-Binding Proteins Electron Transport Complex IV - metabolism Embryo, Mammalian Eye Proteins - metabolism Fibroblasts - metabolism Hematopoietic stem cells Hematopoietic Stem Cells - physiology Homeodomain Proteins - metabolism HSP70 Heat-Shock Proteins - deficiency Immunohistochemistry - methods Immunoprecipitation - methods In Situ Nick-End Labeling - methods Intermediate Filament Proteins - metabolism Isoenzymes - metabolism Liver - cytology Liver - growth & development Liver - metabolism Membrane Proteins - deficiency Membrane Proteins - physiology Mice Mice, Knockout Motor Neurons - physiology Mutation Nerve Tissue Proteins - metabolism Nestin Neurobiology Neurofilament Proteins - metabolism Neurons Neurosciences Paired Box Transcription Factors PAX6 Transcription Factor Physiological aspects Propidium Protein-Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins B-raf - metabolism Proto-Oncogene Proteins c-akt Rats Repressor Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction - methods RNA, Messenger - biosynthesis RNA, Small Interfering - metabolism Spinal Cord - cytology Spinal Cord - growth & development Spinal Cord - metabolism Transcription Factors Transfection - methods Germany
ISSN:	1097-6256, 1546-1726
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-6256 1546-1726
DOI:	10.1038/nn1524