Regulation of the Cdc25A gene by the human papillomavirus Type 16 E7 oncogene.
Cdc25A is a tyrosine phosphatase that is involved in the regulation of the G1/S phase transition by activating cyclin E/Cdk2 and cyclin A/Cdk2 complexes through removal of inhibitory phosphorylations. The E6 and E7 oncoproteins of the high-risk human papillomaviruses (HPV) interact with and functionally abrogate the p53 and pRB proteins, respectively. In the present study we have investigated the regulation of the Cdc25A promoter during G1 and S-phases of the cell cycle and by the HPV-16 E7 oncoprotein. Serum induction leads to a derepression of the Cdc25A promoter and can be mediated through two E2F binding sites, E2F-A and E2F-C. While E2F-A is by both E2F1 and E2F4, E2F-C is regulated only by E2F1. The Cdc25A promoter is transactivated by the E7 oncogene of HPV-16. Furthermore, Cdc25A levels are highly increased in E7-expressing cell lines. Inducible expression of E7 leads to an immediate increase in Cdc25A protein levels. These data suggest that Cdc25A may be a critical target of HPV-16 E7 in the disruption of the G1/S phase transition.
Katich
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SC
Angewandte Tumorvirologie (F0400), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
Zerfass-Thome
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K
Hoffmann
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I
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000235:genetics*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; C493754:E2f1 protein, mouse; C493763:E2f4 protein, mouse; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; C517004:CDC25A protein, human; C517005:Cdc25a protein, mouse; D020687:cdc25 Phosphatases