Ubiquitin Proteasome System (UPS): What Can Chromatin Do for You?

Curr Opin Cell Biol. 2007 Apr;19(2):206-14. doi: 10.1016/j.ceb.2007.02.014. Epub 2007 Feb 20.


Cul4-Ddb1, a RING H2 ubiquitin ligase, plays an important role in many vital cellular processes including DNA replication, DNA repair and transcription. Recent research reveals strong links between Cul4-mediated signaling pathways and chromatin biology. Ubiquitylation of substrates by Cul4-Ddb1 occurs on chromatin and is initiated by chromatin-based signals that either recruit Cul4-Ddb1 to chromatin or alter the activity of the ligase. This includes Cul4-mediated ubiquitylation of the replication licensing factor, Cdt1; a process that requires chromatin-bound PCNA and Cdt2, a member of the recently identified family of candidate substrate receptors for Cul4 (termed Ddb1- and Cul4-associated factors: DCAFs). The activity of two other Cul4-based ubiquitin ligases, Cul4-Ddb1(Ddb2) and Cul4-Ddb1(CSA), are differentially regulated by the COP9 signalosome in response to different chromatin-based signals. Finally, examples of direct modifications to chromatin by Cul4-Ddb1 have emerged, including ubiquitylation of histones and the recruitment of enzymes involved in chromatin remodeling or histone methylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • COP9 Signalosome Complex
  • Chromatin / metabolism*
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism
  • DNA Damage
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Histones / metabolism
  • Humans
  • Multiprotein Complexes / metabolism
  • Peptide Hydrolases / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Signal Transduction / physiology*
  • Transcription, Genetic
  • Ubiquitin / metabolism*


  • Chromatin
  • Cullin Proteins
  • DNA-Binding Proteins
  • Histones
  • Multiprotein Complexes
  • Proliferating Cell Nuclear Antigen
  • Ubiquitin
  • Peptide Hydrolases
  • COP9 Signalosome Complex
  • Proteasome Endopeptidase Complex