Interaction of BAG1 and Hsp70 mediates neuroprotectivity and increases chaperone activity
2005 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Liman, J., Ganesan, S., Dohm, C. P., Krajewski, S., Reed, J. C., Bähr, M., Wouters, F. S. ... Kermer, P. (2005). Interaction of BAG1 and Hsp70 mediates neuroprotectivity and increases chaperone activity. Molecular and Cellular Biology, 25(9), 3715-3725. doi: https://doi.org/10.1128/MCB.25.9.3715-3725.2005
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- Authors
- Liman, Jan ; Ganesan, Sundar; Dohm, Christoph Peter ; Krajewski, S.; Reed, John C.; Bähr, Mathias ; Wouters, Fred S. ; Kermer, Pawel
- Abstract
- It was recently shown that Bcl-2-associated athanogene 1 (BAG1) is a potent neuroprotectant as well as a marker of neuronal differentiation. Since there appears to exist an equilibrium within the cell between BAG1 binding to heat shock protein 70 (Hsp70) and BAG1 binding to Raf-1 kinase, we hypothesized that changing BAG1 binding characteristics might significantly alter BAG1 function. To this end, we compared rat CSM14.1 cells and human SHSY-5Y cells stably overexpressing full-length BAG1 or a deletion mutant (BAG Delta C) no longer capable of binding to Hsp70. Using a novel yellow fluorescent protein-based foldase biosensor, we demonstrated an upregulation of chaperone in situ activity in cells overexpressing full-length BAG1 but not in cells overexpressing BAG Delta C compared to wild-type cells. Interestingly, in contrast to the nuclear and cytosolic localizations of full-length BAG1, BAG Delta C was expressed exclusively in the cytosol. Furthermore, cells expressing BAG Delta C were no longer protected against cell death. However, they still showed accelerated neuronal differentiation. Together, these results suggest that BAG1-induced activation of Hsp70 is important for neuroprotectivity, while BAG1-dependent modulation of neuronal differentiation in vitro is not.
- Issue Date
- 2005
- Journal
- Molecular and Cellular Biology
- ISSN
- 0270-7306