An Hsp90 co-chaperone links protein folding and degradation and is part of a conserved protein quality control

• In this paper, we show that the essential Hsp90 co-chaperone Sgt1 is a member of a general protein quality control network that links folding and degradation through its participation in the degradation of misfolded proteins both in the cytosol and the endoplasmic reticulum (ER). Sgt1-dependent protein degradation acts in a parallel pathway to the ubiquitin ligase (E3) and ubiquitin chain elongase (E4), Hul5, and overproduction of Hul5 partly suppresses defects in cells with reduced Sgt1 activity. Upon proteostatic stress, Sgt1 accumulates transiently, in an Hsp90- and proteasome-dependent manner, with quality control sites (Q-bodies) of both yeast and human cells that co-localize with Vps13, a protein that creates organelle contact sites. Misfolding disease proteins, such as synphilin-1 involved in Parkinson's disease, are also sequestered to these compartments and require Sgt1 for their clearance. © 2021 The Author(s)

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Nyckelord

26S proteasome

aging

chaperone

Hsp90

Hul5

protein quality control

proteostasis

Sgt1

heat shock protein 90

Hul5 protein

peptides and proteins

proteasome

protein serine threonine kinase

Sgt1 protein

synphilin 1

ubiquitin protein ligase

ubiquitin protein ligase E3

unclassified drug

Vps13 protein

Article

cell growth

controlled study

cytosol

endoplasmic reticulum

enzyme activity

HeLa cell line

human

human cell

nonhuman

Parkinson disease

protein aggregation

protein degradation

protein expression

protein folding

protein homeostasis

protein localization

protein quality

yeast cell

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)