Emerging roles of deubiquitinases in cancer-associated pathways.
Deubiquitinases (DUBs) are emerging as important regulators of many pathways germane to cancer. They may regulate the stability of key oncogenes, exemplified by USP28 stabilisation of c-Myc. Alternatively they can negatively regulate ubiquitin-dependent signalling cascades such as the NF-kappaB activation pathway. We review the current literature that associates DUBs with cancer and discuss their suitability as drug targets of the future.
Sacco
Joseph J
JJ
Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Liverpool, L69 3BX, UK.
Coulson
Judy M
JM
Clague
Michael J
MJ
Urbé
Sylvie
S
D000818:Animals; D002268:Carboxypeptidases / Q000502:physiology; D003528:Carcinoma, Adenoid Cystic / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D000074749:Deubiquitinating Enzyme CYLD; D010450:Endopeptidases / Q000502:physiology*; D005199:Fanconi Anemia / Q000503:physiopathology; D064429:Fatty Acid Synthases / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000502:physiology; D016259:Genes, myc / Q000502:physiology; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D009857:Oncogenes / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000502:physiology; D010447:Peptide Hydrolases; D011471:Prostatic Neoplasms / Q000503:physiopathology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases; D051153:Wnt Proteins
D051858:Forkhead Transcription Factors; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C482860:UCHL1 protein, human; C442902:USP28 protein, human; C486203:USP4 protein, human; C506234:USP9X protein, human; D025801:Ubiquitin; D051153:Wnt Proteins; D064429:Fatty Acid Synthases; D044767:Ubiquitin-Protein Ligases; D020794:Receptor Protein-Tyrosine Kinases; D051059:PTEN Phosphohydrolase; D002268:Carboxypeptidases; D010450:Endopeptidases; D010447:Peptide Hydrolases; C476302:STAMBPL1 protein, human; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; C421245:UCHL5 protein, human; C108665:USP2 protein, human; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases