Roles of ubiquitin signaling in transcription regulation.
Rivaling or cooperating with other post-translational modifications, ubiquitination plays central roles in regulating numerous cellular processes. Not surprisingly, gain- or loss-of-function mutations in several components of the ubiquitin system are causally linked to human pathologies including cancer. The covalent attachment of ubiquitin to target proteins occurs in sequential steps and involves ubiquitin ligases (E3s) which are the most abundant enzymes of the ubiquitin system. Although often associated with proteasomal degradation, ubiquitination is also involved in regulatory events in a proteasome-independent manner. Moreover, ubiquitination is reversible and specific proteases, termed deubiquitinases (DUBs), remove ubiquitin from protein substrates. While we now appreciate the importance of ubiquitin signaling in coordinating a plethora of physio-pathological processes, the molecular mechanisms are not fully understood. This review summarizes current findings on the critical functions exerted by E3s and DUBs in transcriptional control, particularly chromatin remodeling and transcription initiation/elongation.
Maisonneuve-Rosemont Hospital Research Center, Department of Medicine and Department of Biochemistry, University of Montréal, Montréal, Canada.
Ian
I
Hammond-Martel
Maisonneuve-Rosemont Hospital Research Center, Department of Medicine and Department of Biochemistry, University of Montréal, Montréal, Canada.
Helen
H
Yu
Maisonneuve-Rosemont Hospital Research Center, Department of Medicine and Department of Biochemistry, University of Montréal, Montréal, Canada. Electronic address: aelbachir.hmr@ssss.gouv.qc.ca.
El Bachir
EB
Affar
D000818:Animals; D002450:Cell Communication; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics*
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex