EBV LMP-1 negatively regulates expression and pro-apoptotic activity of Par-4 in nasopharyngeal carcinoma cells.
Latent membrane protein-1 (LMP-1) of the Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), and in this study we sought to determine whether the pro-apoptotic activity of prostate apoptosis response-4 (Par-4) is modulated by LMP-1 in NPC cells. We found that LMP-1 diminished the pro-apoptotic activity of Par-4 and negatively regulated Par-4 protein by de novo synthesis; moreover, although LMP-1 accelerated a Par-4 activator, PKA, we demonstrated that LMP-1 also activated the PI3K/Akt pathway and increased Bcl-2 expression to suppress the activity of Par-4. Consequently, our results revealed a novel negative action of LMP-1 on the pro-apoptosis protein Par-4 by the coordination of multiple signaling pathways.
Lee
Jeng-Woei
JW
Department and Institute of Life Science, College of Life Science, Tzu-Chi University, No. 701, Zhongyang Rd., Sec. 3, Hualien 97004, Taiwan. jwlee@mail.tcu.edu.tw
Liu
Po-Fan
PF
Hsu
Lee-Ping
LP
Chen
Peir-Rong
PR
Chang
Chung-Hsing
CH
Shih
Wen-Ling
WL
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000502:physiology*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014763:Viral Matrix Proteins / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019253:Proto-Oncogene Proteins c-bcl-2; D014763:Viral Matrix Proteins; C101296:prostate apoptosis response-4 protein; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases