title: Epstein-Barr virus-encoded LMP1 triggers regulation of the ERK-mediated Op18/stathmin signaling pathway in association with cell cycle.
abstract: The MAPKs are activated by a variety of cellular stimuli to participate in a series of signaling cascades and mediate diverse intracellular responses. One potential target of the MAPKs is Op18/stathmin, a molecule that acts as an integrator of diverse cell signaling pathways and regulates the dynamics of microtubules, which are involved in modulating a variety of cellular processes, including cell cycle progression and cell growth. Our study focused on the regulation of the MAPK-mediated Op18/stathmin signaling pathway, which is triggered by the Epstein-Barr virus-encoded latent membrane protein 1 ( LMP1) oncogene in nasopharyngeal carcinoma cells. The results showed that the activity of MAPK, which was induced by LMP1, varied with cell cycle progression; LMP1 upregulated phosphorylation of ERK during the G(1)/S phase, but negatively regulated phosphorylation of ERK during the G(2)/M phase. We found that the regulation of Op18/stathmin signaling by LMP1 was mainly mediated through ERK. The inhibition of LMP1 expression attenuated the interaction of ERK with Op18/stathmin and promoted microtubule depolymerization. These findings indicate the existence of a new cell cycle-associated signaling pathway in which LMP1 regulates ERK-mediated Op18/stathmin signaling.
authors.affiliation: Cancer Research Institute, Changsha, China.
authors.forename: Xuechi
authors.initials: X
authors.lastname: Lin
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Tao
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Sufang
authors.initials: S
authors.lastname: Liu
authors.forename: Lili
authors.initials: L
authors.lastname: Guo
authors.forename: Zijian
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D002277:Carcinoma; D002453:Cell Cycle; D045744:Cell Line, Tumor; D021881:DNA, Catalytic / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System; D008870:Microtubules / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D021881:DNA, Catalytic; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D050777:Stathmin; D014763:Viral Matrix Proteins; D048049:Extracellular Signal-Regulated MAP Kinases