Identification of major phosphorylation sites of Epstein-Barr virus nuclear antigen leader protein (EBNA-LP): ability of EBNA-LP to induce latent membrane protein 1 cooperatively with EBNA-2 is regulated by phosphorylation

Journal of Virology
A YokoyamaYasushi Kawaguchi

Abstract

Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a phosphoprotein suggested to play important roles in EBV-induced immortalization of B cells. One of the potential functions of EBNA-LP is a cooperative induction with EBNA-2 of viral and cellular gene expression, including that of the genes for viral latent membrane protein 1 (LMP-1) and cellular cyclin D2. We report here that the phosphorylation of EBNA-LP by cellular kinase(s) is critical to its ability to cooperate with EBNA-2 in up-regulating the expression of LMP-1 in a B-lymphoma cell line. Our conclusion is based on the following observations. (i) Mass-spectrometric analysis of purified EBNA-LP and mutational analyses of EBNA-LP revealed that the serine residue at position 35 in the W2 repeat domain is the major phosphorylation site of EBNA-LP in vivo. (ii) Substitutions of this site in each W2 repeat domain with alanine markedly reduced the ability of the protein to induce LMP-1 expression in combination with EBNA-2 in Akata cells. (iii) Replacement at the major phosphorylation sites with glutamic acids restored the wild-type phenotype. It is well established that this substitution mimics constitutive phosphorylation. These results indicated that the ...Continue Reading

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Citations

Nov 17, 2006·Journal of Virology·Yoshihiro IzumiyaHsing-Jien Kung
Mar 16, 2007·Journal of Virology·Edward GershburgJoseph S Pagano
Mar 8, 2007·Blood·Chih-Wen PengElliott Kieff
Jan 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chih-Wen PengShizuko Harada
Sep 24, 2005·The EMBO Journal·Paul D LingDonald B Bloch
Dec 2, 2004·Experimental Cell Research·Elena KashubaLaszlo Szekely
Nov 6, 2018·Medical Microbiology and Immunology·Huali YinRunliang Gan
Aug 15, 2003·Oncogene·Soumen ChakrabortyGiuseppina Nucifora
Sep 3, 2010·Science Signaling·Daniel Schwartz, George M Church

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