Cellular Targets of EBV-encoded Nuclear Antigens (EBNAs) and Their Involvement in Virus-Induced Tran

来源 :BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会) | 被引量 : 0次 | 上传用户:kona
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  EBV is one of the most highly transforming viruses known.The EBV-immortalized B-cells use a viral program, designated as type Ⅲ that is not used in any other cells.They express six virally encoded nuclear proteins (EBNA1-6) and three membrane proteins (LMP1, LMP2A and B).The mechanism of transformation is not understood in detail, but it is clear that the virus exploits the normal signaling pathways of the B lymphocyte.The six growth transformation associated viral proteins (EBNA-1,-2,-3,-5,-6 and LMP1) promote cell proliferation and protect from apoptosis.DNA damage, oncogene activation and other types of cellular stress induce p53 dependent G1 arrest or apoptosis.Human DNA tumor viruses inactivate the p53 pathway as part of their primary strategy.Human papilloma virus encodes the E6 antigen that binds to p53 and to the cellular ubiquitin-protein ligase E3A.This binding leads to polyubiquitination of p53 and its proteasomal degradation.Large T encoded by Simian virus 40 binds to the DNA-binding domain of p53 and abolishes its functional activity.The transactivation activity of p53 is also blocked by HHV8 encoded LANA protein and the functionally corresponding ORF73 of Herpesvirus Saimiri.
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