Epstein-Barr virus induces a distinct form of DNA-bound STAT1 compared with that found in interferon-stimulated B lymphocytes.
Since 'constitutive activation' of STAT1 was first described in Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs), there has been controversy regarding the molecular identity of the STAT1 DNA-binding complex found in these cells. The post-translational modifications of STAT1 in LCLs have been analysed and an LMP1-induced STAT1 DNA-binding complex, different from that generated by alpha interferon (IFN) stimulation and not involving tyrosine phosphorylation, is demonstrated. STAT1 is serine-phosphorylated downstream of PI3K and MEK in LCLs and this modification restricts IFN-stimulated STAT1-DNA binding. These data suggest that EBV induces a distinct form of DNA-bound STAT1 in virus-infected cells.
McLaren
James
J
Department of Medical Biochemistry and Immunology, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Rowe
Martin
M
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Brennan
Paul
P
Department of Medical Biochemistry and Immunology, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
D000107:Acetylation; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D008239:Lysine / Q000737:chemistry; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007370:Interferon Type I; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014763:Viral Matrix Proteins; D014443:Tyrosine; D012694:Serine; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D020930:MAP Kinase Kinase Kinases; D008239:Lysine