Nat Rev Drug Discov. 2006 Jul;5(7):596-613.

Drug discovery in the ubiquitin-proteasome system.

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Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

Abstract

Regulated protein turnover via the ubiquitin-proteasome system (UPS) underlies a wide variety of signalling pathways, from cell-cycle control and transcription to development. Recent evidence that pharmacological inhibition of the proteasome can be efficacious in the treatment of human cancers has set the stage for attempts to selectively inhibit the activities of disease-specific components of the UPS. Here, we review recent advances linking UPS components with specific human diseases, most prominently cancer and neurodegenerative disorders, and emphasize potential sites of therapeutic intervention along the regulated protein-degradation pathway.

PMID:: 16816840; [PubMed - indexed for MEDLINE]

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R01 AG011085-18/AG/NIA NIH HHS/United States

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