title: Cellular responses to misfolded proteins and protein aggregates.
abstract: Maintenance of the proteome is a major homeostatic task of the cell and disregulation of protein homeostasis can be deadly. The accumulation of different forms of misfolded protein can perturb protein homeostasis and cause extensive cell and tissue damage. The cell has various quality control systems to help prevent the accumulation of misfolded proteins and the complexity of the different mechanisms that have evolved is bewildering. The first order of business for all quality control systems is recognition of misfolded proteins, which is followed by a triage decision. In many cases, modular molecular chaperones function in different assemblies with degradatory or folding co-factors to direct a misfolded protein toward continued life or death. Herein, an overview of quality control mechanisms that triage soluble cytosolic proteins, protein aggregates, and ER-associated proteins is presented.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Houck
authors.forename: Sangita
authors.initials: S
authors.lastname: Singh
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Cyr
mesh_terms: D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D057165:Proteostasis Deficiencies / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; D044767:Ubiquitin-Protein Ligases