title: 14-3-3 and aggresome formation: implications in neurodegenerative diseases.
abstract: Protein misfolding and aggregation underlie the pathogenesis of many neurodegenerative diseases. In addition to chaperone-mediated refolding and proteasomal degradation, the aggresome-macroautophagy pathway has emerged as another defense mechanism for sequestration and clearance of toxic protein aggregates in cells. Previously, the 14-3-3 proteins were shown to be indispensable for the formation of aggresomes induced by mutant huntingtin proteins. In a recent study, we have determined that 14-3-3 functions as a molecular adaptor to recruit chaperone-associated misfolded proteins to dynein motors for transport to aggresomes. This molecular complex involves a dimeric binding of 14-3-3 to both the dynein-intermediate chain (DIC) and an Hsp70 co-chaperone Bcl-2-associated athanogene 3 (BAG3). As 14-3-3 has been implicated in various neurodegenerative diseases, our findings may provide mechanistic insights into its role in managing misfolded protein stress during the process of neurodegeneration.
authors.affiliation: Department of Biomedical Sciences; Florida State University College of Medicine; Tallahassee, FL USA; Guang An Men Hospital; Beijing PR China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Biomedical Sciences; Florida State University College of Medicine; Tallahassee, FL USA.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biomedical Sciences; Florida State University College of Medicine; Tallahassee, FL USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D048948:14-3-3 Proteins / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D017510:Protein Folding
chemical_list: D048948:14-3-3 Proteins
keywords: 14-3-3; aggresomes; chaperones; inclusion bodies; neurodegeneration; protein aggregation; protein misfolding