Regulation of proteasome activity in health and disease

Marion Schmidt, Daniel Finley

Research output: Contribution to journalReview articlepeer-review

322 Scopus citations


The ubiquitin-proteasome system (UPS) is the primary selective degradation system in the nuclei and cytoplasm of eukaryotic cells, required for the turnover of myriad soluble proteins. The hundreds of factors that comprise the UPS include an enzymatic cascade that tags proteins for degradation via the covalent attachment of a poly-ubiquitin chain, and a large multimeric enzyme that degrades ubiquitinated proteins, the proteasome. Protein degradation by the UPS regulates many pathways and is a crucial component of the cellular proteostasis network. Dysfunction of the ubiquitination machinery or the proteolytic activity of the proteasome is associated with numerous human diseases. In this review we discuss the contributions of the proteasome to human pathology, describe mechanisms that regulate the proteolytic capacity of the proteasome, and discuss strategies to modulate proteasome function as a therapeutic approach to ameliorate diseases associated with altered UPS function. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.

Original languageEnglish (US)
Pages (from-to)13-25
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number1
StatePublished - Jan 2014
Externally publishedYes


  • Proteasome
  • Protein degradation
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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