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BAG3 mediates chaperone‐based aggresome‐targeting and selective autophagy of misfolded proteins
Author(s) -
Gamerdinger Martin,
Kaya A Murat,
Wolfrum Uwe,
Clement Albrecht M,
Behl Christian
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.203
Subject(s) - aggresome , bag3 , autophagy , microbiology and biotechnology , chaperone (clinical) , biology , dynein , hsp70 , microtubule , heat shock protein , ubiquitin , chemistry , biochemistry , medicine , apoptosis , pathology , gene
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.