Phosphorylation and nuclear translocation of STAT3 regulated by the Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma

  • Authors:
    • Yi-ping Liu
    • Yun-nian Tan
    • Zhen-lian Wang
    • Liang Zeng
    • Zhong-xin Lu
    • Li-li Li
    • Wei Luo
    • Min Tang
    • Ya Cao
  • View Affiliations

  • Published online on: February 1, 2008     https://doi.org/10.3892/ijmm.21.2.153
  • Pages: 153-162
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Abstract

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) oncoprotein has been shown to mediate activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we delineated the mechanism by which LMP1 stimulates STAT3 in a human nasopharyngeal carcinoma (NPC) cell line. LMP1 stimulated STAT3 Tyr 705-dependent nuclear accumulation, as well as the phosphorylation of STAT3 at both Tyr 705 and Ser 727. Treatment of cells with interleukin-6 neutralizing antibody inhibited the phosphorylation of STAT3 Tyr 705 and Ser 727. The differential phosphorylation of STAT3 was found to be a result of activation of Janus kinase 3 (JAK3) and extracellular signal-regulated kinase (ERK). The biological significance of JAK3-mediated activation of STAT3 Tyr 705 phosphorylation was further assessed by treating the cells with an inhibitor (WHI-P131) of JAK3. Inhibition of ERK activity by an inhibitor (PD98059) of MAPK/extracellular signal-regulated kinase kinase (MEK1) decreased the LMP1-induced activation of STAT3 Ser 727. Furthermore, immunohistochemical analysis showed an increased nuclear STAT3 Tyr 705 staining in LMP1-positive cells and STAT3 Tyr 705 phosphorylation related to NPC stages III and IV. Demonstration of the involvement of different kinases in LMP1-induced STAT3 activation supports the involvement of the JAK/STAT and mitogen-activated protein kinase (MAPK)/ERK signaling pathways in the regulation of STAT3 activation by LMP1.

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February 2008
Volume 21 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Liu Y, Tan Y, Wang Z, Zeng L, Lu Z, Li L, Luo W, Tang M and Cao Y: Phosphorylation and nuclear translocation of STAT3 regulated by the Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma. Int J Mol Med 21: 153-162, 2008
APA
Liu, Y., Tan, Y., Wang, Z., Zeng, L., Lu, Z., Li, L. ... Cao, Y. (2008). Phosphorylation and nuclear translocation of STAT3 regulated by the Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma. International Journal of Molecular Medicine, 21, 153-162. https://doi.org/10.3892/ijmm.21.2.153
MLA
Liu, Y., Tan, Y., Wang, Z., Zeng, L., Lu, Z., Li, L., Luo, W., Tang, M., Cao, Y."Phosphorylation and nuclear translocation of STAT3 regulated by the Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma". International Journal of Molecular Medicine 21.2 (2008): 153-162.
Chicago
Liu, Y., Tan, Y., Wang, Z., Zeng, L., Lu, Z., Li, L., Luo, W., Tang, M., Cao, Y."Phosphorylation and nuclear translocation of STAT3 regulated by the Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma". International Journal of Molecular Medicine 21, no. 2 (2008): 153-162. https://doi.org/10.3892/ijmm.21.2.153