Transcription factor AP-2 mRNA and DNA binding activity are constitutively expressed in SV40-immortalized but not normal human lung fibroblasts.
Large T antigen (LT) expressed by the oncogenic DNA virus SV40 transforms cells by interacting with and perturbing the normal function of several important cellular proteins including P53, RB, c-MYC, and AP-2. AP-2 binds to regulatory elements within the SV40 enhancer and is therefore of particular interest for mechanisms relating to viral transcription, replication, and packaging. LT antigen has been previously shown to inhibit transcription factor AP-2 from binding to its cognate cis-element in DNA in vitro, and this is believed to occur through a direct physical interaction between the LT and AP-2 proteins. Recently LT and AP-2 were shown to interact at the protein level in vivo and this interaction appeared to mediated by the RB protein. Although LT inhibited AP-2 DNA binding in vitro, the effects of LT on AP-2 expression and DNA binding activity in vivo have not been previously reported. We report here that transcription factor AP-2alpha is constitutively expressed in SV40-transformed cells compared to their normal cell counterparts. The overexpression of AP-2alpha in SV40 transformed cells occurred at the levels of mRNA, protein, and DNA binding activity. The increase in AP-2 DNA binding in vivo was particularly interesting since previous studies in vitro would have predicted that AP-2 DNA binding should be decreased in the presence of LT. AP-2 is a plieotropic regulator of gene expression, activating some and repressing others. Thus, increased cellular AP-2 activity may be an important downstream effector for the transforming ability of SV40.
Huang
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Department of Radiology, The University of Iowa, Iowa City, Iowa, 52242, USA.
Domann
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FE
D000957:Antigens, Viral, Tumor / Q000378:metabolism; D002472:Cell Transformation, Viral / Q000235:genetics*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics* / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D015854:Up-Regulation
D000957:Antigens, Viral, Tumor; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors