Functional similarity between HPV16E7, SV40 large T and adenovirus E1a proteins

We have analysed the immortalizing function of Human Papillomavirus type 16 (HPV16) in a rat cell line which has been derived by immortalizing rat embryo fibroblasts with a thermolabile SV40 large T antigen and is temperature sensitive for growth. Introduction of wild type SV40 large T antigen or the adenovirus E1a 12s gene product has previously been shown to readily overcome the inability of these cells to divide at the non-permissive temperature. In contrast, the introduction of myc, another known immortalizing gene, cannot complement the growth defect of these cells. This cell line therefore provides a novel assay system which can distinguish two groups of immortalizing oncogenes. We have shown here that expression of HPV16 can readily complement the growth defect in this rat cell line and that this function can be genetically localised to E7. Cells expressing HPV16 E6 sequences are also weakly rescued from growth arrest at the non-permissive temperature. These results demonstrate a functional similarity between HPV16 E7, SV40 large T and adenovirus E1a and suggest that these genes may immortalize cells by a common mechanism. Interestingly, the limited sequence homology between these three gene products is restricted to the domain which has recently been implicated in binding the retinoblastoma gene product.