A Census of Hsp70-Mediated Proteome Solubility Changes upon Recovery from Heat Stress

Eukaryotic cells respond to heat
shock through several regulatory
processes including upregulation of stress responsive chaperones and
reversible shutdown of cellular activities through formation of protein
assemblies. However, the underlying regulatory mechanisms of the recovery
of these heat-induced protein assemblies remain largely elusive. Here,
we measured the proteome abundance and solubility changes during recovery
from heat shock in the mouse Neuro2a cell line. We found that prefoldins
and translation machinery are rapidly down-regulated as the first
step in the heat shock response. Analysis of proteome solubility reveals
that a rapid mobilization of protein quality control machineries,
along with changes in cellular energy metabolism, translational activity,
and actin cytoskeleton are fundamental to the early stress responses.
In contrast, longer term adaptation to stress involves renewal of
core cellular components. Inhibition of the Hsp70 family, pivotal
for the heat shock response, selectively and negatively affects the
ribosomal machinery and delays the solubility recovery of many nuclear
proteins. ProteomeXchange: PXD030069.