| Literature DB >> 26858444 |
Chih-Lung Shen1, Cheng-Der Liu1, Ren-In You2, Yung-Hao Ching3, Jun Liang4, Liangru Ke4, Ya-Lin Chen5, Hong-Chi Chen5, Hao-Jen Hsu5, Je-Wen Liou6, Elliott Kieff7, Chih-Wen Peng8.
Abstract
Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriP-mediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.Entities:
Keywords: EBNA1; EBV; NCL; RPL4; oriP
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Year: 2016 PMID： 26858444 PMCID： PMC4776490 DOI： 10.1073/pnas.1525444113
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205