title: Cancer-testis antigen MAGE-C2 binds Rbx1 and inhibits ubiquitin ligase-mediated turnover of cyclin E.
abstract: Cancer-testis antigen MAGE-C2 is normally expressed in testis but aberrantly expressed in various kinds of tumors. Its functions in tumor cells are mostly unknown. Here, we show that MAGE-C2 binds directly to the RING domain protein Rbx1, and participates in Skp1-Cullin1-F box protein (SCF) complex. Furthermore, MAGE-C2 can inhibit the E3 ubiquitin ligase activity of SCF complex. Ablation of endogenous MAGE-C2 decreases the level of cyclin E and accelerates cyclin E turnover by inhibiting ubiquitin-mediated proteasome degradation. Overexpression of MAGE-C2 increases the level of cyclin E and promotes G1-S transition and cell proliferation, and the results are further confirmed by knockdown of MAGE-C2. Overall, the study indicates that MAGE-C2 is involved in SCF complex and increases the stability of cyclin E in tumor cells.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Chengli
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D016193:G1 Phase / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D016196:S Phase / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D002352:Carrier Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D019927:Cyclin E; C405429:MAGEC2 protein, human; D009363:Neoplasm Proteins; C479529:RBX1 protein, human; D044843:SKP Cullin F-Box Protein Ligases
keywords: MAGE-C2; SCF complex; cancer-testis antigen; cell cycle; cyclin E