Hsp70 - a master regulator in protein degradation

FEBS Lett. 2017 Sep;591(17):2648-2660. doi: 10.1002/1873-3468.12751. Epub 2017 Jul 25.

Abstract

Proteostasis, the controlled balance of protein synthesis, folding, assembly, trafficking and degradation, is a paramount necessity for cell homeostasis. Impaired proteostasis is a hallmark of ageing and of many human diseases. Molecular chaperones are essential for proteostasis in eukaryotic cells, and their function has traditionally been linked to protein folding, assembly and disaggregation. More recent findings suggest that chaperones also contribute to key steps in protein degradation. In particular, Hsp70 has an essential role in substrate degradation through the ubiquitin-proteasome system, as well as through different autophagy pathways. Accumulated knowledge suggests that the fate of an Hsp70 substrate is dictated by the combination of partners (cochaperones and other chaperones) that interact with Hsp70 in a given cell context.

Keywords: Hsp70; protein degradation; proteostasis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Protein Domains
  • Proteolysis*

Substances

  • HSP70 Heat-Shock Proteins

Associated data

  • PDB/4JNE
  • PDB/2KHO