The POU domain protein Tst-1 and papovaviral large tumor antigen function synergistically to stimulate glia-specific gene expression of JC virus.
Synergism between transcriptional activators is a powerful way of potentiating their function. Here we show that the glial POU domain protein Tst-1 (also known as Oct-6 and SCIP) and large tumor antigen (T antigen) synergistically increased transcription from both the early and the late promoters of papovavirus JC in glial cells. Synergism between both proteins did not require T-antigen-mediated DNA replication or direct binding of T antigen to the promoter. The ability of T antigen to functionally cooperate with Tst-1 was contained within its N-terminal region, shown by the fact that small tumor antigen (t antigen) could substitute for T antigen in transfection experiments. In addition to this functional synergism, a direct interaction between Tst-1 and T antigen was observed in vitro. Using deletion mutants of Tst-1 and T antigen, the POU domain of Tst-1 and the N-terminal region of T antigen were found to participate in this interaction. Because of the low levels of Tst-1 present in oligodendrocytes, synergism between Tst-1 and T antigen could be an important factor in establishing the lytic infection of oligodendrocytes by JC virus during the course of the fatal demyelinating disease progressive multifocal leukoencephalopathy.
Zentrum für Molekulare Neurobiologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
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D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D005909:Glioblastoma; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D015151:Immunoblotting; D007577:JC Virus / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016296:Mutagenesis; D050816:Octamer Transcription Factor-6; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D014157:Transcription Factors / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C494178:POU3F1 protein, human; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; D008156:Luciferases; D005982:Glutathione Transferase