Abstract
THE transforming proteins of several DNA tumour viruses, including adenovirus Ela and simian virus 40 large T antigen, complex with the retinoblastoma (Rb) tumour-suppressor gene product1,2. This requires regions in these viral proteins necessary for transformation and is thought to inactivate the growth-suppressing properties trf the Rb protein by disrupting its interaction with cellular targets3. Indeed, regions of Rb required to form a complex with Ela and large T antigen are often mutated in transformed cells4. The level at which the Rb protein regulates proliferation is unknown, although one possibility is transcription. We have previously characterized a sequence-specific transcription factor, DRTF1, the activity of which is downregulated as embryonal carcinoma stem cells differentiate. DRTF1 is found in several discrete protein complexes (a, b and c) which are of different sizes but have the same DNA specificity5,6. We now show that one of these also contains the Rb protein and, further, that the adenovirus E1a protein causes the dissociation of the Rb protein from this complex. This requires conserved regions 1 and 2 of E1a that are known to be required for efficient transformation7. These results demonstrate that the Rb protein forms a complex with a DNA-bound transcription factor, and suggests that the Rb protein might act by regulating transcription.
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Bandara, L., La Thangue, N. Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor. Nature 351, 494–497 (1991). https://doi.org/10.1038/351494a0
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DOI: https://doi.org/10.1038/351494a0
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