Drug discovery in the ubiquitin - Proteasome system

Grzegorz Nalepa, Mark Rolfe, J. Wade Harper

Research output: Contribution to journalArticle

459 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)596-613
Number of pages18
JournalNature Reviews Drug Discovery
Issue number7
StatePublished - Jul 1 2006

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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