title: Inhibition of the NEDD8 conjugation pathway by shRNA to UBA3, the subunit of the NEDD8-activating enzyme, suppresses the growth of melanoma cells.
abstract: Neural precursor cell-expressed developmentally down-regulated 8 (NEDD8), a ubiquitin-like protein, mainly functions through covalent ligation to cullin proteins. Conjugation of NEDD8 with cullins can promote ubiquitination, which plays a critical role in the degradation of many proteins. UBA3 is the subunit of NEDD8- activating enzyme which is one of the keys for NEDD8 linkage to cullin proteins. Previous research showed NEDD8 conjugation to be up-regulated in highly proliferative cell lines. In the present study, up-regulated NEDD8 conjugation was observed in melanoma cell lines by Western blot analysis. After down-regulation with a RNAi to UBA3, proliferation of M14 was suppressed in vitro and in vivo. In conclusion, up-regulated NEDD8 conjugation may be involved in the development of melanoma. Interference in this pathway might offera promising method for melanoma therapy.
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cheng
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Ruo-Hong
authors.initials: RH
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Jian-Fang
authors.initials: JF
authors.lastname: Sun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D000075687:NEDD8 Protein; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014452:Ubiquitins; D044764:Ubiquitin-Activating Enzymes; C491802:NAE protein, human