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PMID: 20053547 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

A cellular perspective on conformational disease: the role of genetic background and proteostasis networks.

Current opinion in structural biology ·Vol. 20 ·No. 1 ·2010-02-00 ·Pages 23-32

Gidalevitz T, Kikis EA, Morimoto RI

Abstract

The inherently error-prone nature of protein biosynthesis and turnover leads to a constant flux of destabilized proteins. Genetic mutations in conformational disease-associated proteins, as well as exposure to acute and chronic proteotoxic stresses, further increase the load of misfolded protein on the proteostasis network. During aging, this leads to enhanced instability of the proteome, failure to buffer destabilizing genetic mutations or polymorphisms, and cellular decline. The combination of cell-type-specific differences in the buffering capacity of the proteostasis network and destabilizing polymorphisms in the genetic background may account for some of the cell-type specificity observed in disease, even when the predominant disease-associated protein is widely expressed.

MeSH Terms
Animals Cells/metabolism,pathology Disease/genetics Homeostasis Humans Molecular Chaperones/metabolism Protein Conformation Proteins/chemistry,genetics,metabolism
Chemicals
Molecular Chaperones Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Gidalevitz Tali
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA.
Kikis Elise A
Morimoto Richard I
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Article Info
Journal
Current opinion in structural biology
Abbr.
Curr Opin Struct Biol
ISSN
1879-033X
DOI
10.1016/j.sbi.2009.11.001
Published
2010-02-00
Epub
2010-00-05
Pages
23-32
Language
English
Region
England
NLM ID
9107784
PMCID
PMC3050498
Subset
IM
Grants
NIA NIH HHS · R01 AG026647 · United States
NIA NIH HHS · R01 AG026647-05 · United States
NIGMS NIH HHS · R37 GM038109 · United States
NIGMS NIH HHS · R37 GM038109-23 · United States
External Links
PubMed source DOI: 10.1016/j.sbi.2009.11.001 PMC Full Text View journal details
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