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Figure 5 | Cancer Cell International

Figure 5

From: Transformation of SV40-immortalized human uroepithelial cells by 3-methylcholanthrene increases IFN- and Large T Antigen-induced transcripts

Figure 5

Tag binds to and inactivates many host proteins, especially p53 and pRB. Binding blocks pRB-mediated cell-cycle arrest and p53-mediated apoptosis. When E2F is not bound by pRB, it dimerizes with DP1 and DP2, initiating transcription of cell-cycle progression genes. PKR binds and is activated by the presence of double-stranded RNA, and activates pathways leading to apoptosis. Bound PKR activates NFκB, causing dissociation from IκB. The transcription factor NFκB binds cellular DNA and stimulates transcription of target genes resulting in either proliferation or apoptosis. Phosphorylation of PKR is initiated by binding to ds RNA, and PKR then causes eIF2a, an initiator of transcription that stimulates viral protein transcription/translation, to be released from its inactive state. Tag can also act on eIF2a causing downstream rescue of translation of viral proteins. Tag recruits SP1, a transcription factor that, together with DNA primase and ligase, initiates more Tag transcription, as well as of genes under the control of Tag. Tag also recruits RNase L-inactivator. The latter acts on ds viral RNA and converts it to inactive ss RNA, and is pro-apoptotic. The active homodimer of endonuclease RNase L is activated by 2'-5' OAS 1 & 2. See Table S1 (Additional File 1) and text for genes altered in this study.

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