There is a reciprocal change in the expression of two members of the BAG 
(Bcl-2-associated athanogen) family, BAG1 and BAG3, during cellular aging and 
under acute stress ("BAG1-BAG3-switch"). BAG3 was recently described as a 
mediator of a novel macroautophagy pathway that uses the specificity of heat 
shock protein 70 (HSP70) to misfolded proteins and also involves other protein 
partners, such as HSPB8. Also crucial for induction and execution of autophagy 
are sequestosome-1/p62 (SQSTM1/p62) and LC3, an autophagosome-associated 
protein. In this novel pathway, BAG3 mediates the targeting and transport of 
degradation-prone substrates into aggresomes via the microtubule-motor dynein. 
Interestingly, aggresome-targeting by BAG3 does not depend on substrate 
ubiquitination and is, therefore, involved in the clearance of misfolded 
proteins that are not ubiquitinated.