SV40 large T-antigen: dual oncogene.
Simian virus 40 (SV40) is a small, DNA-containing tumour virus. One of its gene products, the large tumour antigen (T-ag), is essential for both viral replication and cell transformation. SV40 T-ag can be considered a dual oncogene protein; it is a composite transforming protein that provides distinct functions at different subcellular locations. In addition to its roles in virus replication, T-ag exerts numerous effects on host cells. Those cellular effects reflect viral stimulation of host cell entry into S phase. Numerous chemical modifications have been ascribed to T-ag. They might be involved in defining subpopulations of T-ag that are, in turn, responsible for mediating various T-ag biochemical functions. The T-ag polypeptide, 90,000-100,000 in molecular weight, appears to contain multiple, discrete functional domains; several biological activities have been assigned to relatively small defined regions of the molecule. The cellular progenitors of the T-ag biochemical activities are not obvious. A cellular protein, p53, thought to be involved in regulation of cell proliferation, becomes complexed with T-ag in transformed cells and is stabilized. The interaction of T-ag with this cellular substrate may play an important part in SV40 transformation. T-ag and T-ag/p53 complexes are localized in both the nucleus and plasma membrane of transformed cells. T-ag is transported to the nucleus because of a 7-residue nuclear transport signal contained within its primary sequence. Its migration to the membrane is by an unknown pathway. Only a minor fraction of the total cellular T-ag is present at the cell surface. Both amino and carboxy termini of the T-ag polypeptide are exposed on the extracellular face of the cell. Nuclear and membrane T-ag are structurally very similar, although a portion of membrane T-ag is acylated and nuclear T-ag is not. The nuclear and membrane forms of T-ag apparently provide separate and complementary functions necessary for cell transformation. Nuclear T-ag is important in immortalizing primary cells and membrane T-ag may mediate more pronounced morphological changes. A model is presented, postulating how the two forms of T-ag might cooperate to mediate phenotypic transformation.
D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D004261:DNA Replication; D005796:Genes; D005814:Genes, Viral; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009857:Oncogenes; D011494:Protein Kinases / Q000235:genetics*; D013539:Simian virus 40 / Q000235:genetics*; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D009856:Oncogene Proteins, Viral; D011494:Protein Kinases