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Cold Spring Harb Perspect Biol. 2019 Nov 1;11(11). pii: a033902. doi: 10.1101/cshperspect.a033902.

Recognition and Degradation of Mislocalized Proteins in Health and Disease.

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Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.


A defining feature of eukaryotic cells is the segregation of complex biochemical processes among different intracellular compartments. The protein targeting, translocation, and trafficking pathways that sustain compartmentalization must recognize a diverse range of clients via degenerate signals. This recognition is imperfect, resulting in polypeptides at incorrect cellular locations. Cells have evolved mechanisms to selectively recognize mislocalized proteins and triage them for degradation or rescue. These spatial quality control pathways maintain cellular protein homeostasis, become especially important during organelle stress, and might contribute to disease when they are impaired or overwhelmed.

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