Trans-activation of the adenovirus E2 promoter by human papillomavirus type 16 E7 is mediated by retinoblastoma-dependent and -independent pathways.
In common with the adenovirus E1A and simian virus 40 large T oncoproteins, the E7 protein of human papillomavirus (HPV) type 16 interacts with the retinoblastoma (Rb) tumour suppressor protein (pRb). The functional importance of this interaction for HPV-16 E7 protein was investigated by analysis of the transactivating function of E7 at the adenovirus E2 promoter in a set of breast tumour cell lines. Trans-activation by HPV-16 E7 in two pRb-deficient cell lines demonstrated that pRb is not essential for E7-mediated trans-activation, but reconstitution of Rb expression indicated the existence of an Rb-mediated pathway of E7 trans-activation. This pathway results from suppression by E7 of a trans-repressing function encoded by the Rb gene. The E7 protein is shown to be capable of interacting in vivo with the Rb-related protein p107. Furthermore, analysis of a fusion construct between the amino terminus of Rb and the carboxy terminus of p107 suggests that, in common with pRb, the p107 protein trans-represses the adenovirus E2 early promoter. Therefore it is proposed that the pRb-independent pathway of E7 trans-activation is a consequence of the suppression of trans-repression by p107.
Carlotti
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F
Cambridge University Department of Pathology, U.K.
Crawford
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L
D017502:Adenovirus E2 Proteins / Q000235:genetics*; D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D016160:Retinoblastoma Protein / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D014407:Tumor Cells, Cultured
D017502:Adenovirus E2 Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; C059731:oncogene protein E7, Human papillomavirus type 16