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.

Author affiliations

1. Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
2. Current address: Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University, 1044 West Walnut Street, R4/402A, Indianapolis, Indiana 46202, USA.
3. Millennium Pharmaceuticals Inc., 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA.

Correspondence to: J. Wade Harper¹ Email: wade_harper@hms.harvard.edu

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