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Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function.
Proc Natl Acad Sci U S A. 2016 Feb 23; 113(8):2229-34.PN

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.

Authors+Show Affiliations

Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan;Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan;Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Sec. 3, Hualien 97004, Taiwan;Department of Molecular Biology and Human Genetics, Tzu Chi University, Sec. 3, Hualien 97004, Taiwan;Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115;Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115;Department of Life Sciences, Tzu Chi University, Sec. 3, Hualien 97004, Taiwan;Department of Life Sciences, Tzu Chi University, Sec. 3, Hualien 97004, Taiwan;Department of Life Sciences, Tzu Chi University, Sec. 3, Hualien 97004, Taiwan;Institute of Biochemical Sciences, Tzu Chi University, Sec. 3, Hualien 97004, Taiwan.Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115; ekieff@rics.bwh.harvard.edu pengcw@mail.tcu.edu.tw.Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan; Department of Life Sciences, Tzu Chi University, Sec. 3, Hualien 97004, Taiwan; ekieff@rics.bwh.harvard.edu pengcw@mail.tcu.edu.tw.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26858444

Citation

Shen, Chih-Lung, et al. "Ribosome Protein L4 Is Essential for Epstein-Barr Virus Nuclear Antigen 1 Function." Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 8, 2016, pp. 2229-34.
Shen CL, Liu CD, You RI, et al. Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function. Proc Natl Acad Sci U S A. 2016;113(8):2229-34.
Shen, C. L., Liu, C. D., You, R. I., Ching, Y. H., Liang, J., Ke, L., Chen, Y. L., Chen, H. C., Hsu, H. J., Liou, J. W., Kieff, E., & Peng, C. W. (2016). Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function. Proceedings of the National Academy of Sciences of the United States of America, 113(8), 2229-34. https://doi.org/10.1073/pnas.1525444113
Shen CL, et al. Ribosome Protein L4 Is Essential for Epstein-Barr Virus Nuclear Antigen 1 Function. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2229-34. PubMed PMID: 26858444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function. AU - Shen,Chih-Lung, AU - Liu,Cheng-Der, AU - You,Ren-In, AU - Ching,Yung-Hao, AU - Liang,Jun, AU - Ke,Liangru, AU - Chen,Ya-Lin, AU - Chen,Hong-Chi, AU - Hsu,Hao-Jen, AU - Liou,Je-Wen, AU - Kieff,Elliott, AU - Peng,Chih-Wen, Y1 - 2016/02/08/ PY - 2016/2/10/entrez PY - 2016/2/10/pubmed PY - 2016/7/28/medline KW - EBNA1 KW - EBV KW - NCL KW - RPL4 KW - oriP SP - 2229 EP - 34 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 113 IS - 8 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/26858444/Ribosome_Protein_L4_is_essential_for_Epstein_Barr_Virus_Nuclear_Antigen_1_function_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=26858444 DB - PRIME DP - Unbound Medicine ER -