Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein-Barr virus encoded latent membrane protein 1.
Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is essential for the immortalization of human B cells and is linked etiologically to several human tumors. LMP1 is an integral membrane protein which acts like a constitutively active receptor. It binds tumor necrosis factor (TNF)-receptor-associated factors (TRAFs), activates NFkappaB and triggers the transcription factor activating protein-1 (AP-1) via the c-Jun N-terminal kinase (JNK) cascade, but its specific contribution to AP-1 has not been elucidated fully. Members of AP-1 family, the Jun and fos related protein, have been shown to directly interact and form heterodimeric complexes. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser63, ser73) and Jun B involved in the process of the new heterodimeric form. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer form of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma.
Song
Xin
X
Cancer Research Institute, Xiangya School of Medicine, Central South of University, 88 Xiangya Road, Changsha 410078, China.
Tao
Yong-Guang
YG
Deng
Xi-Yun
XY
Jin
Xin
X
Tan
Yun-Nian
YN
Tang
Min
M
Wu
Qiao
Q
Lee
Leo M
LM
Cao
Ya
Y
D019281:Dimerization; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014763:Viral Matrix Proteins; D048031:JNK Mitogen-Activated Protein Kinases