of it, is typically kept active by a positive feedback loop. Inactivation of p53 Viruses employ various methods of inactivating p53. The adenovirus E1B protein (55K) prevents p53 from regulating genes by binding to the site on p53 which binds to the genome. In SV40, the large T antigen (LT) is an analogue; LT also binds to several other cellular proteins, such as p107 and p130, on the same residues. LT binds to p53's binding domain on the DNA (rather than on the protein), again preventing p53 from appropriately regulating genes. HPV instead degrades p53: the HPV protein E6 binds to a cellular protein called the E6-associated protein (E6-AP, also known as UBE3A), forming a complex which causes the rapid and specific ubiquitination of p53. Inactivation of Rb Rb is inactivated (thereby allowing the G1/S transition to progress unimpeded) by different but analogous viral oncoproteins. The adenovirus early region 1A (E1A) is an oncoprotein which binds to Rb and can stimulate transcription and transform cells. SV40 uses the same protein for inactivating Rb, LT, to inactivate p53. HPV contains a protein, E7, which can bind to Rb in much the same way. Rb can be inactivated by phosphorylation, or by being bound to a viral oncoprotein, or by mutations—mutations which prevent oncoprotein binding are also associated with cancer. Variations DNA oncoviruses typically cause cancer by inactivating p53 and Rb, thereby allowing unregulated cell division and creating tumors. There may be many different mechanisms which have evolved separately; in addition to those described above, for example, the Human Papillomavirus inactivates p53 by sequestering it in the cytoplasm. SV40 has been well studied and does not cause cancer in humans, but a recently discovered analogue called Merkel cell polyomavirus has been associated with Merkel cell carcinoma, a form of skin cancer. The Rb binding feature is believed to be the same between the two viruses. RNA oncoviruses In the 1960s, the replication process of RNA virus was believed to be similar to other single-stranded RNA. Single-stranded RNA replication involves RNA-dependent RNA synthesis which meant that virus-coding enzymes would make partial double-stranded RNA. This belief was proven to be incorrect because there were no double-stranded RNA found in the retrovirus cell. In 1964, Howard Temin proposed a provirus hypothesis, but shortly after reverse transcription in the retrovirus genome was discovered. Description of virus All retroviruses have three major coding domains; gag, pol and