Distinct Modes of Regulation of the Uch37 Deubiquitinating Enzyme in the Proteasome and in the Ino80 Chromatin-Remodeling Complex

Tingting Yao, Ling Song, Jingji Jin, Yong Cai, Hidehisa Takahashi, Selene K. Swanson, Michael P. Washburn, Laurence Florens, Ronald C. Conaway, Robert E. Cohen, Joan W. Conaway

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Deubiquitinating enzymes (DUBs) are proteases that can antagonize ubiquitin-mediated signaling by disassembling ubiquitin-protein conjugates. How DUBs are regulated in vivo and how their substrate specificities are achieved are largely unknown. The conserved DUB Uch37 is found on proteasomes in organisms ranging from fission yeast to humans. Deubiquitination by Uch37 is activated by proteasomal binding, which enables Uch37 to process polyubiquitin chains. Here we show that in the nucleus Uch37 is also associated with the human Ino80 chromatin-remodeling complex (hINO80). In hINO80, Uch37 is held in an inactive state; however, it can be activated by transient interaction of the Ino80 complex with the proteasome. Thus, DUB activities can be modulated both positively and negatively via dynamic interactions with partner proteins. In addition, our findings suggest that the proteasome and the hINO80 chromatin-remodeling complex may cooperate to regulate transcription or DNA repair, processes in which both complexes have been implicated.

Original languageEnglish (US)
Pages (from-to)909-917
Number of pages9
JournalMolecular cell
Volume31
Issue number6
DOIs
StatePublished - Sep 26 2008
Externally publishedYes

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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