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ErbB4 (JM-b/CYT-1)-induced expression and phosphorylation of c-Jun is abrogated by human papillomavirus type 16 E5 protein

Oncogene volume 26, pages 42–53 (2007)Cite this article

Abstract

Human papillomavirus type 16 E5 (HPV-16 E5) is a highly hydrophobic membrane protein with weak-transforming activity, which is associated with ErbB4 receptor in HPV-16-infected cervical lesions. Presently, we investigated the transforming mechanisms of E5 involving ErbB4 signaling. Firstly, we report a role for ErbB4 (JM-b/CYT-1) receptor that activates c-jun gene expression and phosphorylating at Ser63 and Ser73 of the c-Jun protein in ligand-independent and Ras-c-jun NH2-terminal kinase-dependent pathway. Secondly, we show that HPV-16 E5 protein can form a complex with ErbB4 via binding to the extracellular and transmembrane domains of ErbB4 (JM-b/CYT-1). When co-expressing HPV-16 E5 and ErbB4 in cells, E5 can abrogate ErbB4-induced c-Jun protein expression and phosphorylation resulted in increasing cell proliferation compared to ErbB4-expressing cells. The interaction between of HPV-16 E5 and ErbB4 provides more insight into the mechanisms of HPV-16 E5 transformation induction.

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Acknowledgements

This work was supported by National Health Research Institute NHRI-EX93-9314BI, and National Science Council Grant NSC 93-2320-B-016-008 and 93-3112-B-016-005. We are indebted to Ms Yung-Lu Lee and Mr David D Cheng for technical assistance.

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Authors and Affiliations

  1. Department of Microbiology, Gradurate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan

    S-L Chen & S-T Lin

  2. Department of Microbiology and Immunology, National Defense Medical Center, National Defense University, Taipei, Taiwan

    S-L Chen & W-C Hsiao

  3. Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan

    T-C Tsai

  4. Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan

    Y-P Tsao

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  1. S-L Chen
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  2. S-T Lin
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Correspondence to S-L Chen.

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Chen, SL., Lin, ST., Tsai, TC. et al. ErbB4 (JM-b/CYT-1)-induced expression and phosphorylation of c-Jun is abrogated by human papillomavirus type 16 E5 protein. Oncogene 26, 42–53 (2007). https://doi.org/10.1038/sj.onc.1209768

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