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Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome.

Recruitment of substrates to the 26S proteasome usually requires covalent attachment of the Lys48-linked polyubiquitin chain. In contrast, modifications with the Lys63-linked polyubiquitin chain and/or monomeric ubiquitin are generally thought to function in proteasome-independent cellular processes. Nevertheless, the ubiquitin chain-type specificity for the proteasomal targeting is still poorly understood, especially in vivo. Using mass spectrometry, we found that Rsp5, a ubiquitin-ligase in budding yeast, catalyzes the formation of Lys63-linked ubiquitin chains in vitro. Interestingly, the 26S proteasome degraded well the Lys63-linked ubiquitinated substrate in vitro. To examine whether Lys63-linked ubiquitination serves in degradation in vivo, we investigated the ubiquitination of Mga2-p120, a substrate of Rsp5. The polyubiquitinated p120 contained relatively high levels of Lys63-linkages, and the Lys63-linked chains were sufficient for the proteasome-binding and subsequent p120-processing. In addition, Lys63-linked chains as well as Lys48-linked chains were detected in the 26S proteasome-bound polyubiquitinated proteins. These results raise the possibility that Lys63-linked ubiquitin chain also serves as a targeting signal for the 26S proteaseome in vivo.

Pubmed ID: 19153599


  • Saeki Y
  • Kudo T
  • Sone T
  • Kikuchi Y
  • Yokosawa H
  • Toh-e A
  • Tanaka K


The EMBO journal

Publication Data

February 18, 2009

Associated Grants


Mesh Terms

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Lysine
  • Mass Spectrometry
  • Membrane Proteins
  • Models, Biological
  • Plasmids
  • Polyubiquitin
  • Proteasome Endopeptidase Complex
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Signal Transduction
  • Trans-Activators
  • Transcription Factors
  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • p120 GTPase Activating Protein