Preparing your results

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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.

Pubmed ID: 23843611


  • Xu Z
  • Graham K
  • Foote M
  • Liang F
  • Rizkallah R
  • Hurt M
  • Wang Y
  • Wu Y
  • Zhou Y


Journal of cell science

Publication Data

September 15, 2013

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS50355
  • Agency: NIGMS NIH HHS, Id: R01 GM102115
  • Agency: NIGMS NIH HHS, Id: R15 GM097326

Mesh Terms

  • 14-3-3 Proteins
  • Dyneins
  • Molecular Chaperones
  • Protein Folding
  • Proteins
  • Transfection