Adenovirus type 12 early region 1A expresses a 52R protein repressing the trans-activating activity of transcription factor c-Jun/AP-1.
Oncoproteins of the early transcription unit 1A (E1A) of adenoviruses (Ad) are known to modulate the expression of all viral and of a variety of cellular genes. In this communication we present data demonstrating for the first time an activity associated with a protein (the 52R protein) expressed exclusively from E1A of the highly oncogenic subtype Ad12. The 52R protein, which does not contain any of the conserved regions (CR1-CR3) necessary for the trans-regulatory functions of the larger E1A proteins (266R, 235R), represses the trans-activating activity of the transcription factor c-Jun/AP-1. The repression of c-Jun/AP-1 activity is neither due to a down-regulation of the c-jun transcription rate nor due to an inhibition of binding of the transcription factor complex to its target sequence, at least under the conditions of in vitro band shift assays. As the 52R protein is most probably not associated with DNA-bound c-Jun/AP-1, we suppose that it represses c-Jun activity either by a squelching mechanism sequestering a cofactor, which is an essential link between c-Jun/AP-1 and the components of the basal transcriptional machinery or by modifying post-translational modifications necessary for the trans-activation function of c-Jun.
Brockmann
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Institute of Molecular Biology (Cancer Research), Medical School Essen, FRG.
Feng
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Kröner
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Tries
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B
Esche
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H
D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015967:Gene Expression Regulation, Viral; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012097:Repressor Proteins / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000187:drug effects*
D017500:Adenovirus E1A Proteins; D010703:Phorbol Esters; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators