Abstract
The accumulation and aggregation of misfolded proteins is the primary hallmark for more than 45 human degenerative diseases. These devastating disorders include Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Over 15 degenerative diseases are associated with the aggregation of misfolded proteins specifically in the nucleus of cells. However, how the cell safeguards the nucleus from misfolded proteins is not entirely clear. In this review, we discuss what is currently known about the cellular mechanisms that maintain protein homeostasis in the nucleus and protect the nucleus from misfolded protein accumulation and aggregation. In particular, we focus on the chaperones found to localize to the nucleus during stress, the ubiquitin–proteasome components enriched in the nucleus, the signaling systems that might be present in the nucleus to coordinate folding and degradation, and the sites of misfolded protein deposition associated with the nucleus.
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References
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Acknowledgments
We tried to cite all primary literature pertaining to nuclear PQC. We apologize to any colleagues if we unintentionally missed their studies. This work was supported by an NIH/NIA grant R01AG031136 (R.G.G.), an Ellison Medical Foundation New Scholar Award in Aging (R.G.G), an Israel Science Foundation Grant ISF 843/11 (D.K), a German–Israel Foundation Grant GIF I-1201-242.13/2012 (D.K.), an ERC-StG2013 337713 DarkSide grant (D.K.), and an American Federation for Aging Research grant (D.K.).
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Gallagher, P.S., Oeser, M.L., Abraham, Ac. et al. Cellular maintenance of nuclear protein homeostasis. Cell. Mol. Life Sci. 71, 1865–1879 (2014). https://doi.org/10.1007/s00018-013-1530-y
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DOI: https://doi.org/10.1007/s00018-013-1530-y