Next Article in Journal
Local Order in the Unfolded State: Conformational Biases and Nearest Neighbor Interactions
Next Article in Special Issue
Emerging Mechanistic Insights into AAA Complexes Regulating Proteasomal Degradation
Previous Article in Journal
New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases
Previous Article in Special Issue
Assembly Mechanisms of Specialized Core Particles of the Proteasome
Article Menu

Export Article

Open AccessReview
Biomolecules 2014, 4(3), 704-724; doi:10.3390/biom4030704

Chaperoning Proteins for Destruction: Diverse Roles of Hsp70 Chaperones and their Co-Chaperones in Targeting Misfolded Proteins to the Proteasome

Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat-Ram, Jerusalem 91904, Israel
*
Author to whom correspondence should be addressed.
Received: 28 March 2014 / Revised: 31 May 2014 / Accepted: 24 June 2014 / Published: 17 July 2014
(This article belongs to the Special Issue Proteasomes and Its Regulators)
View Full-Text   |   Download PDF [2034 KB, uploaded 17 July 2014]   |  

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. View Full-Text
Keywords: the Ub-proteasome system; molecular chaperones; protein misfolding; protein degradation; protein aggregation; yeast; Hsp40; Hsp70 the Ub-proteasome system; molecular chaperones; protein misfolding; protein degradation; protein aggregation; yeast; Hsp40; Hsp70
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Shiber, A.; Ravid, T. Chaperoning Proteins for Destruction: Diverse Roles of Hsp70 Chaperones and their Co-Chaperones in Targeting Misfolded Proteins to the Proteasome. Biomolecules 2014, 4, 704-724.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top