Functional Modules of the Proteostasis Network

Cells invest in an extensive network of factors to maintain protein homeostasis (proteostasis) and prevent the accumulation of potentially toxic protein aggregates. This proteostasis network (PN) comprises the machineries for the biogenesis, folding, conformational maintenance, and degradation of pr...

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Bibliographic Details
Published in:Cold Spring Harbor perspectives in biology 2020-01, Vol.12 (1), p.a033951
Main Authors: Jayaraj, Gopal G, Hipp, Mark S, Hartl, F Ulrich
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Chaperones
Differentiation (biology)
Homeostasis
Humans
Mammalian cells
Molecular Chaperones - chemistry
Neurodegenerative diseases
Neurodegenerative Diseases - metabolism
PERSPECTIVES
Protein Conformation
Protein Denaturation
Protein Folding
Proteins
Proteins - chemistry
Proteome - metabolism
Proteomes
Proteostasis - physiology
Thermodynamics
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Summary:Cells invest in an extensive network of factors to maintain protein homeostasis (proteostasis) and prevent the accumulation of potentially toxic protein aggregates. This proteostasis network (PN) comprises the machineries for the biogenesis, folding, conformational maintenance, and degradation of proteins with molecular chaperones as central coordinators. Here, we review recent progress in understanding the modular architecture of the PN in mammalian cells and how it is modified during cell differentiation. We discuss the capacity and limitations of the PN in maintaining proteome integrity in the face of proteotoxic stresses, such as aggregate formation in neurodegenerative diseases. Finally, we outline various pharmacological interventions to ameliorate proteostasis imbalance.
ISSN:1943-0264
1943-0264
DOI:10.1101/cshperspect.a033951