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: Xuechi Lin, Min Tang, Yongguang Tao, Lili Li, Sufang Liu, Lili Guo, Zijian Li, Xiaoqian Ma, Juan Xu, Ya Cao
• Journal: Cancer science (Cancer Sci) Vol. 103 Issue 6 Pg. 993-9 (Jun 2012) ISSN: 1349-7006 [Electronic] England
• PMID: 22417000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Japanese Cancer Association.

Chemical References

• DNA, Catalytic
• EBV-associated membrane antigen, Epstein-Barr virus
• Oncogene Proteins, Viral
• RNA, Small Interfering
• Receptors, Cell Surface
• Stathmin
• Viral Matrix Proteins
• Extracellular Signal-Regulated MAP Kinases

Topics

• Carcinoma
• Cell Cycle
• Cell Line, Tumor
• DNA, Catalytic (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Herpesvirus 4, Human (genetics)
• Humans
• MAP Kinase Signaling System
• Microtubules (metabolism)
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (metabolism, pathology)
• Oncogene Proteins, Viral (genetics, metabolism)
• RNA Interference
• RNA, Small Interfering
• Receptors, Cell Surface
• Stathmin (genetics, metabolism)
• Viral Matrix Proteins (genetics, metabolism)