Ubiquitin proteasome system (UPS): what can chromatin do for you?
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.
O'Connell
Brenda C
BC
Department of Pathology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115, USA.
Harper
J Wade
JW
D000818:Animals; D000075686:COP9 Signalosome Complex; D002843:Chromatin / Q000378:metabolism*; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D002843:Chromatin; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D018809:Proliferating Cell Nuclear Antigen; D025801:Ubiquitin; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D046988:Proteasome Endopeptidase Complex