How the nucleus copes with proteotoxic stress.
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.
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
Yoko
Y
Shibata
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA. Electronic address: r-morimoto@northwestern.edu.
Richard I
RI
Morimoto
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D012568:Schizosaccharomyces / Q000737:chemistry / Q000378:metabolism
D005656:Fungal Proteins