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Cell. 2015 Sep 10;162(6):1286-98. doi: 10.1016/j.cell.2015.08.041.

Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress.

Author information

1
Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
2
Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
3
FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
4
Department of Statistics, Harvard University, Cambridge, MA 02138, USA.
5
FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA; Department of Statistics, Harvard University, Cambridge, MA 02138, USA.
6
Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA. Electronic address: dadrummond@uchicago.edu.

Abstract

Heat causes protein misfolding and aggregation and, in eukaryotic cells, triggers aggregation of proteins and RNA into stress granules. We have carried out extensive proteomic studies to quantify heat-triggered aggregation and subsequent disaggregation in budding yeast, identifying >170 endogenous proteins aggregating within minutes of heat shock in multiple subcellular compartments. We demonstrate that these aggregated proteins are not misfolded and destined for degradation. Stable-isotope labeling reveals that even severely aggregated endogenous proteins are disaggregated without degradation during recovery from shock, contrasting with the rapid degradation observed for many exogenous thermolabile proteins. Although aggregation likely inactivates many cellular proteins, in the case of a heterotrimeric aminoacyl-tRNA synthetase complex, the aggregated proteins remain active with unaltered fidelity. We propose that most heat-induced aggregation of mature proteins reflects the operation of an adaptive, autoregulatory process of functionally significant aggregate assembly and disassembly that aids cellular adaptation to thermal stress.

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PMID:
26359986
PMCID:
PMC4567705
DOI:
10.1016/j.cell.2015.08.041
[Indexed for MEDLINE]
Free PMC Article

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