Chaperoning proteins for destruction: Diverse roles of Hsp70 chaperones and their co-chaperones in targeting misfolded proteins to the proteasome

Ayala Shiber, Tommer Ravid*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations

Abstract

Molecular chaperones were originally discovered as heat shock-induced proteins that facilitate proper folding of proteins with non-native conformations. While the function of chaperones in protein folding has been well documented over the last four decades, more recent studies have shown that chaperones are also necessary for the clearance of terminally misfolded proteins by the Ub-proteasome system. In this capacity, chaperones protect misfolded degradation substrates from spontaneous aggregation, facilitate their recognition by the Ub ligation machinery and finally shuttle the ubiquitylated substrates to the proteasome. The physiological importance of these functions is manifested by inefficient proteasomal degradation and the accumulation of protein aggregates during ageing or in certain neurodegenerative diseases, when chaperone levels decline. In this review, we focus on the diverse roles of stress-induced chaperones in targeting misfolded proteins to the proteasome and the consequences of their compromised activity. We further discuss the implications of these findings to the identification of new therapeutic targets for the treatment of amyloid diseases.

Original languageAmerican English
Pages (from-to)704-724
Number of pages21
JournalBiomolecules
Volume4
Issue number3
DOIs
StatePublished - 1 Sep 2014

Bibliographical note

Publisher Copyright:
© 2014 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

  • Hsp40
  • Hsp70
  • Molecular chaperones
  • Protein aggregation
  • Protein degradation
  • Protein misfolding
  • The Ub-proteasome system
  • Yeast

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