TY - JOUR
T1 - How the nucleus copes with proteotoxic stress
AU - Shibata, Yoko
AU - Morimoto, Richard I.
N1 - Funding Information:
Y.S. is an HHMI postdoctoral fellow of the Damon Runyon Cancer Foundation (DRG 2086-11). R.I.M. is supported by the Ellison Medical Foundation, the Daniel F. and Ada L. Rice Foundation, the Chicago Biomedical Consortium, and NIH grants GM038109, GM081192, AG026647 and NS047331.
PY - 2014/5/19
Y1 - 2014/5/19
N2 - The proper folding of proteins is continuously challenged by intrinsic and extrinsic stresses, and the accumulation of toxic misfolded proteins is associated with many human diseases. Eukaryotic cells have evolved a complex network of protein quality control pathways to protect the proteome, and these pathways are specialized for each subcellular compartment. While many details have been elucidated for how the cytosol and endoplasmic reticulum counteract proteotoxic stress, relatively little is known about the pathways protecting the nucleus from protein misfolding. Proper maintenance of nuclear proteostasis has important implications in preserving genomic integrity, as well as for aging and disease. Here, we offer a conceptual framework for how proteostasis is maintained in this organelle. We define the particular requirements that must be considered for the nucleus to manage proteotoxic stress, summarize the known and implicated pathways of nuclear protein quality control, and identify the unresolved questions in the field.
AB - The proper folding of proteins is continuously challenged by intrinsic and extrinsic stresses, and the accumulation of toxic misfolded proteins is associated with many human diseases. Eukaryotic cells have evolved a complex network of protein quality control pathways to protect the proteome, and these pathways are specialized for each subcellular compartment. While many details have been elucidated for how the cytosol and endoplasmic reticulum counteract proteotoxic stress, relatively little is known about the pathways protecting the nucleus from protein misfolding. Proper maintenance of nuclear proteostasis has important implications in preserving genomic integrity, as well as for aging and disease. Here, we offer a conceptual framework for how proteostasis is maintained in this organelle. We define the particular requirements that must be considered for the nucleus to manage proteotoxic stress, summarize the known and implicated pathways of nuclear protein quality control, and identify the unresolved questions in the field.
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U2 - 10.1016/j.cub.2014.03.033
DO - 10.1016/j.cub.2014.03.033
M3 - Review article
C2 - 24845679
AN - SCOPUS:84901012110
VL - 24
SP - R463-R474
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 10
ER -