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.
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Authors | Jiaqing Hao, Xiao Song, Jingjing Wang, Chengli Guo, Yan Li, Bing Li, Yu Zhang, Yanhui Yin |
Journal | Oncotarget
(Oncotarget)
Vol. 6
Issue 39
Pg. 42028-39
(Dec 08 2015)
ISSN: 1949-2553 [Electronic] United States |
PMID | 26540345
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Neoplasm
- Carrier Proteins
- Cullin 1
- Cullin Proteins
- Cyclin E
- MAGEC2 protein, human
- Neoplasm Proteins
- RBX1 protein, human
- SKP Cullin F-Box Protein Ligases
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Topics |
- Animals
- Antigens, Neoplasm
(genetics, metabolism)
- Carrier Proteins
(genetics, metabolism)
- Cell Cycle
(genetics)
- Cell Line, Tumor
- Cell Proliferation
(genetics)
- Cullin Proteins
(genetics, metabolism)
- Cyclin E
(metabolism)
- G1 Phase
(genetics)
- HEK293 Cells
- Humans
- Immunoblotting
- Immunoprecipitation
- Melanoma
(genetics, metabolism, pathology)
- Mice
- Microscopy, Confocal
- Neoplasm Proteins
(genetics, metabolism)
- Protein Binding
- RNA Interference
- S Phase
(genetics)
- SKP Cullin F-Box Protein Ligases
(genetics, metabolism)
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