Chapter 9 - Transcription factors and human disease

Abstract

The ability to affect cellular transcriptional regulatory processes is crucial to the ability of many different viruses to transform cells. The large T oncogenes of the small DNA tumour viruses SV40 and polyoma and the ElA protein of adenovirus can affect cellular gene expression. This ability is essential for the transforming ability of these viruses. Several RNA viruses also have this ability, containing transcription factors which can act as oncogenes, either by promoting the expression of genes required for growth or by inhibiting the expression of genes required for the production of nonproliferating differentiated cells. Although the oncogenes of both DNA and some RNA tumour viruses can affect transcription, their origins are completely different. Thus the oncogenes of the DNA viruses do not have equivalents in cellular DNA and appear to have evolved within the viral genome, the oncogenes of retroviruses have been picked up from the cellular genome. The fact that, despite their diverse origins, both types of oncogenes can affect transcription indicates that the modulation of transcription represents an effective mechanism for the transformation of cells. The conversion of a normal cellular transcription factor into a cancer-causing viral oncogene allows insights to be obtained into the processes whereby oncogenes become activated. In general, such oncogenes, whether they encode growth factors, growth factor receptors or other types of protein, can be activated within a virus either by over-expression driven by a strong retroviral promoter or by mutation.