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Publication : BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins.

First Author  Gamerdinger M Year  2011
Journal  EMBO Rep Volume  12
Issue  2 Pages  149-56
PubMed ID  21252941 Mgi Jnum  J:168838
Mgi Id  MGI:4939083 Doi  10.1038/embor.2010.203
Citation  Gamerdinger M, et al. (2011) BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep 12(2):149-56
abstractText  Increasing evidence indicates the existence of selective autophagy pathways, but the manner in which substrates are recognized and targeted to the autophagy system is poorly understood. One strategy is transport of a particular substrate to the aggresome, a perinuclear compartment with high autophagic activity. In this paper, we identify a new cellular pathway that uses the specificity of heat-shock protein 70 (Hsp70) to misfolded proteins as the basis for aggresome-targeting and autophagic degradation. This pathway is regulated by the stress-induced co-chaperone Bcl-2-associated athanogene 3 (BAG3), which interacts with the microtubule-motor dynein and selectively directs Hsp70 substrates to the motor and thereby to the aggresome. Notably, aggresome-targeting by BAG3 is distinct from previously described mechanisms, as it does not depend on substrate ubiquitination.
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