EBV-encoded LMP1 regulates Op18/stathmin signaling pathway by cdc2 mediation in nasopharyngeal carcinoma cells.
Oncoprotein 18/stathmin (Op18/stathmin) plays a crucial role in maintaining cell biological characteristics by regulating microtubule dynamics, especially entry into mitosis; phosphorylated Op18/stathmin promotes microtubule polymerization to form the mitotic spindle, which is essential for chromosome segregation and cell division. Cdc2 is a critical kinase in starting M phase events in cell-cycle progression and is a positive regulator of the cell cycle. Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncogenic protein that is able to induce carcinogenesis via various signaling pathways. This study focused on regulation by LMP1 of Op18/stathmin signaling in nasopharyngeal carcinoma (NPC) cells and showed that LMP1 regulates Op18/stathmin signaling through cdc2 mediation, LMP1 upregulates cdc2 kinase activity, and Op18/stathmin phosphorylation promotes the interaction of cdc2 with Op18/stathmin and microtubule polymerization during mitosis, and inhibition of LMP1 expression attenuates the interaction of cdc2 and Op18/stathmin and promotes microtubule depolymerization. These results reveal a new pathway via which LMP1 regulates Op18/stathmin signaling by cdc2 mediation; this new signaling pathway not only perfects the LMP1 regulation network but also elucidates the molecular mechanism of LMP1 that leads to carcinogenesis.
Lin
Xuechi
X
Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, People's Republic of China.
Liu
Sufang
S
Luo
Xiangjian
X
Ma
Xiaoqian
X
Guo
Lili
L
Li
Lili
L
Li
Zijian
Z
Tao
Yongguang
Y
Cao
Ya
Y
D016203:CDC2 Protein Kinase; D002453:Cell Cycle; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000037:antagonists & inhibitors / Q000502:physiology*; D018844:Cyclin-Dependent Kinases; D021881:DNA, Catalytic / Q000494:pharmacology; D004854:Herpesvirus 4, Human; D006801:Humans; D008870:Microtubules / Q000502:physiology; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D050777:Stathmin / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000502:physiology*
D019926:Cyclin B; D021881:DNA, Catalytic; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D050777:Stathmin; D014763:Viral Matrix Proteins; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases