2015 Beckman Symposium   

Qianli Wang

Presentation Date:

Qianli Wang

30 - The tumor suppressor p53 activates an Epstein-Barr virus oncogenic protein

University of Nebraska-Lincoln

Biological Sciences

Epstein-Barr virus is known to be the cause of mononucleosis and is also associated with multiple malignancies such as Burkitt's lymphoma and nasopharyngeal carcinoma. A key reason for this is EBV's ability to induce cancer-associate characteristics in cells through a process called transformation that could lead to tumor formation. For EBV induced transformation to occur, the viral latent membrane protein 1 (LMP1) expression is required. On the other hand, the human body has a series of methods to prevent cancer. Among these, DNA damage response (DDR) and p53, an important anti-tumor gene, are major players. The p53 gene is capable of inducing apoptosis, or programed cell death, to prevent cancer formation, and it is known that DDR activates p53 activity. Previous research has shown that LMP1 suppresses P53 functions. However, the relationships between DDR and LMP1 and the effects of p53 on LMP1 are not known. These may further explain EBV€s efficiency as an oncogenic virus. First, we showed that the p53 antitumor gene actually induces the expression of LMP1. Then, using drugs and radiation to simulate DNA damage, we found that DDR can increase LMP1 expression through p53 activity. Also, we have evidence suggesting that the transcription factor IRF5 is one possible intermediate linking p53 and LMP1 expressions. To our knowledge, this is the first case where DDR, through the activity of an anti-tumor gene, increases a viral oncoprotein expression. As a result, these findings imply that DNA damage to an EBV infected cell may sufficiently induce LMP1 expression to cause transformation and tumor formation.

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