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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.
AuthorsJiaqing Hao, Xiao Song, Jingjing Wang, Chengli Guo, Yan Li, Bing Li, Yu Zhang, Yanhui Yin
JournalOncotarget (Oncotarget) Vol. 6 Issue 39 Pg. 42028-39 (Dec 08 2015) ISSN: 1949-2553 [Electronic] United States
PMID26540345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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