ErbB4 (JM-b/CYT-1)-induced expression and phosphorylation of c-Jun is abrogated by human papillomavirus type 16 E5 protein.
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 NH(2)-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.
Chen
S-L
SL
Department of Microbiology, Gradurate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. showlic@ha.mc.ntu.edu.tw
Lin
S-T
ST
Tsai
T-C
TC
Hsiao
W-C
WC
Tsao
Y-P
YP
D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D008856:Microscopy, Fluorescence; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000378:metabolism*; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine / Q000378:metabolism; D000086082:Viroporin Proteins
D017931:DNA Primers; D066246:ErbB Receptors; D009856:Oncogene Proteins, Viral; D016755:Proto-Oncogene Proteins c-jun; D066247:Receptor, ErbB-4; D012694:Serine; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins; C587689:ERBB4 protein, human