Targeting Ubc9 for cancer therapy.
Ubiquitin-conjugating enzyme (Ubc9) was originally thought to be a conjugating enzyme for ubiquitylation, but was later shown to be responsible for the most recently identified type of post-translational modification, (i.e., SUMO [small ubiquitin-related modifier]) conjugation or sumoylation. Like ubiquitylation, sumoylation modulates protein function through post-translational covalent attachment to lysine residues within targeted proteins. However, although ubiquitylation can lead to protein degradation through the 26S proteasome, sumoylation does not cause protein degradation; instead, it has been implicated in other cellular processes, such as regulating the activity of transcription factors, mediating nuclear translocation of proteins or the formation of subnuclear structures. Interestingly, some proteins can be modified at the same lysine residue by both SUMO and ubiquitin, but with distinct functional consequences. Given that many proteins involved in cell-cycle regulation, proliferation, apoptosis and DNA repair are targets for sumoylation, alterations of sumoylation could ultimately have an impact on cell growth, cancer development and drug responsiveness. As Ubc9 is the sole E2-conjugating enzyme required for sumoylation, and, in particular, Ubc9 is upregulated in an increasing number of human malignancies, such as ovarian carcinoma, melanoma and lung adenocarcinoma, it is a potential target for cancer therapy.
Mo
Yin-Yuan
YY
Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University, PO Box 19626, Springfield, IL 62794, USA. ymo@siumed.edu
Moschos
Stergios J
SJ
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D000970:Antineoplastic Agents; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9