Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Protein-linked ubiquitin chain structure restricts activity of deubiquitinating enzymes.

The attachment of lysine 48 (Lys(48))-linked polyubiquitin chains to proteins is a universal signal for degradation by the proteasome. Here, we report that long Lys(48)-linked chains are resistant to many deubiquitinating enzymes (DUBs). Representative enzymes from this group, Ubp15 from yeast and its human ortholog USP7, rapidly remove mono- and diubiquitin from substrates but are slow to remove longer Lys(48)-linked chains. This resistance is lost if the structure of Lys(48)-linked chains is disrupted by mutation of ubiquitin or if chains are linked through Lys(63). In contrast to Ubp15 and USP7, Ubp12 readily cleaves the ends of long chains, regardless of chain structure. We propose that the resistance to many DUBs of long, substrate-attached Lys(48)-linked chains helps ensure that proteins are maintained free from ubiquitin until a threshold of ubiquitin ligase activity enables degradation.

Pubmed ID: 22072716


  • Schaefer JB
  • Morgan DO


The Journal of biological chemistry

Publication Data

December 30, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01-GM053270
  • Agency: NIGMS NIH HHS, Id: R37 GM053270
  • Agency: NCI NIH HHS, Id: T32-CA09043

Mesh Terms

  • Endopeptidases
  • Humans
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Ubiquitin Thiolesterase
  • Ubiquitination