Binding of the Heterogeneous Ribonucleoprotein K (hnRNP K) to the Epstein-Barr Virus Nuclear Antigen 2 (EBNA2) Enhances Viral LMP2A Expression
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- The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2)The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA-antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV-infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties.…
Autor(en): | Henrik Gross, Christine Hennard, Ilias Masouris, Christian Cassel, Stephanie Barth, Ute Stober-Grässer, Alfredo Mamiani, Bodo Moritz, Dirk Ostareck, Antje Ostareck-Lederer, Nils Neuenkirchen, Utz Fischer, Wen Deng, Heinrich Leonhardt, Elfriede Noessner, Elisabeth Kremmer, Friedrich A. Grässer |
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URN: | urn:nbn:de:bvb:20-opus-133707 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Chemie und Pharmazie / Lehrstuhl für Biochemie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | PLoS One |
Erscheinungsjahr: | 2012 |
Band / Jahrgang: | 7 |
Heft / Ausgabe: | 8 |
Originalveröffentlichung / Quelle: | PLoS ONE 7(8): e42106. doi:10.1371/journal.pone.0042106 |
DOI: | https://doi.org/10.1371/journal.pone.0042106 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 572 Biochemie |
Freie Schlagwort(e): | C-MYC; RNA-polymerase-II; SM proteins; down regulation; gene expression; living cells; messenger RNA; motor-neuron protein; protein argentine methyltranserase; splicing factor |
Datum der Freischaltung: | 17.02.2017 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung |