{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:48:25Z","timestamp":1790524105967,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,1,12]],"date-time":"2011-01-12T00:00:00Z","timestamp":1294790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epstein\u2010Barr virus (EBV) is a human tumour virus that efficiently growth\u2010transforms primary human B\u2010lymphocytes <jats:italic>in vitro<\/jats:italic>. The viral nuclear antigen 2 (EBNA2) is essential for immortalisation of B\u2010cells and stimulates viral and cellular gene expression through interaction with DNA\u2010bound transcription factors. Like its cellular homologue Notch, it associates with the DNA\u2010bound repressor RBPJ\u03ba (CSL\/CBF1) thereby converting RBPJ\u03ba into the active state. For instance, both EBNA2 and Notch activate the cellular HES1 promoter. In EBV\u2010transformed lymphocytes, the RNA of the NP9 protein encoded by human endogenous retrovirus HERV\u2010K(HML\u20102) Type 1 is strongly up\u2010regulated. The NP9 protein is detectable both in EBV\u2010positive Raji cells, a Burkitt's lymphoma cell line, and in IB4, an EBV\u2010transformed human lymphoblastoid cell line. NP9 binds to LNX that forms a complex with the Notch regulator Numb. Therefore, the function of NP9 vis\u2010\u00e0\u2010vis Notch and EBNA2 was analysed. Here, we show that NP9 binds to EBNA2 and negatively affects the EBNA2\u2010mediated activation of the viral C\u2010 and LMP2A promoters. In contrast, NP9 did neither interfere in the activation of the HES1 promoter by Notch nor the induction of the viral LMP1 promoter by EBNA2. In an electrophoretic mobility shift analysis, NP9 reduced the binding of EBNA2 to DNA\u2010bound RBPJ\u03ba by about 50%. The down\u2010regulation of EBNA2\u2010activity by NP9 might represent a cellular defence mechanism against viral infection or could, alternatively, represent an adaptation of the virus to prevent excessive viral protein production that might otherwise be harmful for the infected cell.<\/jats:p>","DOI":"10.1002\/ijc.25760","type":"journal-article","created":{"date-parts":[[2010,11,16]],"date-time":"2010-11-16T18:46:24Z","timestamp":1289933184000},"page":"1105-1115","source":"Crossref","is-referenced-by-count":36,"title":["The NP9 protein encoded by the human endogenous retrovirus HERV\u2010K(HML\u20102) negatively regulates gene activation of the Epstein\u2010Barr virus nuclear antigen 2 (EBNA2)"],"prefix":"10.1002","volume":"129","author":[{"given":"Henrik","family":"Gross","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Barth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Pfuhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivienne","family":"Willnecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Spurk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Gurtsevitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elfriede","family":"Noessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Mueller\u2010Lantzsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Kremmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich 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