Cellular and Molecular Life Sciences

, Volume 71, Issue 10, pp 1865–1879 | Cite as

Cellular maintenance of nuclear protein homeostasis

  • Pamela S. Gallagher
  • Michelle L. Oeser
  • Ayelet-chen Abraham
  • Daniel Kaganovich
  • Richard G. Gardner
Review

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.

Keywords

Nucleus Chaperone Ubiquitin-protein ligase Ubiquitin Proteasome Unfolded protein response Misfolded protein Aggregation Inclusion Aggresome JUNQ 

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Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Pamela S. Gallagher
    • 1
  • Michelle L. Oeser
    • 1
    • 2
  • Ayelet-chen Abraham
    • 3
  • Daniel Kaganovich
    • 3
  • Richard G. Gardner
    • 1
    • 2
  1. 1.Department of PharmacologyUniversity of WashingtonSeattleUSA
  2. 2.Molecular and Cellular Biology ProgramUniversity of WashingtonSeattleUSA
  3. 3.Department of Cell and Developmental Biology, Alexander Silberman Institute of Life SciencesHebrew University of JerusalemJerusalemIsrael

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