Journal
JOURNAL OF CELL SCIENCE
Volume 124, Issue 20, Pages 3381-3392Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.089110
Keywords
Human disease; Nucleo-cytoplasmic transport; Protein trafficking; Subcellular protein mislocalization; Theraputic mistargeting; Theraputic rescue
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Funding
- Spanish MEC [BIO2006-02432]
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The eukaryotic cell is organized into membrane-covered compartments that are characterized by specific sets of proteins and biochemically distinct cellular processes. The appropriate subcellular localization of proteins is crucial because it provides the physiological context for their function. In this Commentary, we give a brief overview of the different mechanisms that are involved in protein trafficking and describe how aberrant localization of proteins contributes to the pathogenesis of many human diseases, such as metabolic, cardiovascular and neurodegenerative diseases, as well as cancer. Accordingly, modifying the disease-related subcellular mislocalization of proteins might be an attractive means of therapeutic intervention. In particular, cellular processes that link protein folding and cell signaling, as well as nuclear import and export, to the subcellular localization of proteins have been proposed as targets for therapeutic intervention. We discuss the concepts involved in the therapeutic restoration of disrupted physiological protein localization and therapeutic mislocalization as a strategy to inactivate disease-causing proteins.
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