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14-3-3 protein targets misfolded chaperone-associated proteins to aggresomes.

Title: 14-3-3 protein targets misfolded chaperone-associated proteins to aggresomes.
Name(s): Xu, Zhe, author
Graham, Kourtney, author
Foote, Molly, author
Liang, Fengshan, author
Rizkallah, Raed, author
Hurt, Myra, author
Wang, Yanchang, author
Wu, Yuying, author
Zhou, Yi, author
Type of Resource: text
Genre: Journal Article
Date Issued: 2013-09-15
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The aggresome is a key cytoplasmic organelle for sequestration and clearance of toxic protein aggregates. Although loading misfolded proteins cargos to dynein motors has been recognized as an important step in the aggresome formation process, the molecular machinery that mediates the association of cargos with the dynein motor is poorly understood. Here, we report a new aggresome-targeting pathway that involves isoforms of 14-3-3, a family of conserved regulatory proteins. 14-3-3 interacts with both the dynein-intermediate chain (DIC) and an Hsp70 co-chaperone Bcl-2-associated athanogene 3 (BAG3), thereby recruiting chaperone-associated protein cargos to dynein motors for their transport to aggresomes. This molecular cascade entails functional dimerization of 14-3-3, which we show to be crucial for the formation of aggresomes in both yeast and mammalian cells. These results suggest that 14-3-3 functions as a molecular adaptor to promote aggresomal targeting of misfolded protein aggregates and may link such complexes to inclusion bodies observed in various neurodegenerative diseases.
Identifier: FSU_pmch_23843611 (IID), 10.1242/jcs.126102 (DOI), PMC3772389 (PMCID), 23843611 (RID), 23843611 (EID), jcs.126102 (PII)
Keywords: 14-3-3, Adaptor, Aggresome, BAG3, Dynein
Grant Number: R01 NS050355, R15 GM097326, NS50355
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at
Subject(s): 14-3-3 Proteins/genetics
14-3-3 Proteins/metabolism
Molecular Chaperones/genetics
Molecular Chaperones/metabolism
Protein Folding
Persistent Link to This Record:
Owner Institution: FSU
Is Part Of: Journal of cell science.
Issue: iss. Pt 18, vol. 126

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Xu, Z., Graham, K., Foote, M., Liang, F., Rizkallah, R., Hurt, M., … Zhou, Y. (2013). 14-3-3 protein targets misfolded chaperone-associated proteins to aggresomes. Journal Of Cell Science. Retrieved from