UAF1 is a subunit of multiple deubiquitinating enzyme complexes

J Biol Chem. 2009 Feb 20;284(8):5343-51. doi: 10.1074/jbc.M808430200. Epub 2008 Dec 15.

Abstract

A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific deubiquitinating enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 deubiquitinating enzyme, which regulates the Fanconi anemia pathway by deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit deubiquitinating enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both enzyme complexes, suggesting that this activator protein may regulate a subclass of human deubiquitinating enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human deubiquitinating enzymes and thereby regulate their activity and substrate specificity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Arabidopsis Proteins
  • Endopeptidases / genetics
  • Endopeptidases / isolation & purification
  • Endopeptidases / metabolism*
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism
  • Fanconi Anemia Complementation Group D2 Protein / genetics
  • Fanconi Anemia Complementation Group D2 Protein / isolation & purification
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • HeLa Cells
  • Humans
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / isolation & purification
  • Multienzyme Complexes / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism*
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / isolation & purification
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitin-Specific Proteases
  • Ubiquitination / physiology*

Substances

  • Arabidopsis Proteins
  • FANCD2 protein, human
  • Fanconi Anemia Complementation Group D2 Protein
  • Multienzyme Complexes
  • Nuclear Proteins
  • USP1 associated factor 1, human
  • USP12 protein, human
  • Endopeptidases
  • USP1 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases