Multiple associated proteins regulate proteasome structure and function

David S. Leggett, John Hanna, Anna Borodovsky, Bernat Crosas, Marion Schmidt, Rohan T. Baker, Thomas Walz, Hidde Ploegh, Daniel Finley

Research output: Contribution to journalArticlepeer-review

515 Scopus citations


We have identified proteins that are abundant in affinity-purified proteasomes, but absent from proteasomes as previously defined because elevated salt concentrations dissociate them during purification. The major components are a deubiquitinating enzyme (Ubp6), a ubiquitin-ligase (Hul5), and an uncharacterized protein (Ecm29). Ecm29 tethers the proteasome core particle to the regulatory particle. Proteasome binding activates Ubp6 300-fold and is mediated by the ubiquitin-like domain of Ubp6, which is required for function in vivo. Ubp6 recognizes the proteasome base and its subunit Rpn1, suggesting that proteasome binding positions Ubp6 proximally to the substrate translocation channel. ubp6Δ mutants exhibit accelerated turnover of ubiquitin, indicating that deubiquitination events catalyzed by Ubp6 prevent translocation of ubiquitin into the proteolytic core particle.

Original languageEnglish (US)
Pages (from-to)495-507
Number of pages13
JournalMolecular Cell
Issue number3
StatePublished - Sep 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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