کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3425630 1227293 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Epstein–Barr virus nuclear antigen 3C targets p53 and modulates its transcriptional and apoptotic activities
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Epstein–Barr virus nuclear antigen 3C targets p53 and modulates its transcriptional and apoptotic activities
چکیده انگلیسی

The p53 tumor suppressor gene is one of the most commonly mutated genes in human cancers and the corresponding encoded protein induces apoptosis or cell-cycle arrest at the G1/S checkpoint in response to DNA damage. To date, previous studies have shown that antigens encoded by human tumor viruses such as SV40 large T antigen, adenovirus E1A and HPV E6 interact with p53 and disrupt its functional activity. In a similar fashion, we now show that EBNA3C, one of the EBV latent antigens essential for the B-cell immortalization in vitro, interacts directly with p53. Additionally, we mapped the interaction of EBNA3C with p53 to the C-terminal DNA-binding and the tetramerization domain of p53, and the region of EBNA3C responsible for binding to p53 was mapped to the N-terminal domain of EBNA3C (residues 130–190), previously shown to interact with a number of important cell-cycle components, specifically SCFSkp2, cyclin A, and cMyc. Furthermore, we demonstrate that EBNA3C substantially represses the transcriptional activity of p53 in luciferase based reporter assays, and rescues apoptosis induced by ectopic p53 expression in SAOS-2 (p53−/−) cells. Interestingly, we also show that the DNA-binding ability of p53 is diminished in the presence of EBNA3C. Thus, the interaction between the p53 and EBNA3C provides new insights into the mechanism(s) by which the EBNA3C oncoprotein can alter cellular gene expression in EBV associated human cancers.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 388, Issue 2, 5 June 2009, Pages 236–247
نویسندگان
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