transcribed as a single messenger RNA processed by alternative splicing. The LTag gene is usually encoded in two exons, of which the first overlaps with the gene for the small tumor antigen (STag); as a result, the two proteins share an N-terminal sequence of around 80 residues, while the remaining ~90 residues of STag are unshared. In a few polyomaviruses - most notably murine polyomavirus, the first member of the family discovered and an efficient oncovirus - an additional protein called middle tumor antigen is expressed from the early region and is highly efficient at cellular transformation. Cellular transformation Some, but not all, polyomaviruses are oncoviruses capable of inducing neoplastic transformation in some cells. In oncogenic polyomaviruses, the tumor antigens are responsible for the transformation activity, although the exact molecular mechanisms vary from one virus to another. SV40 The SV40 large T antigen from the SV40 virus is the most well-studied member of the LTag family. SV40, also known as Macaca mulatta polyomavirus 1, natively infects monkeys and does not cause disease; however, it is oncogenic in some rodents and can immortalize some human cells in primary cell culture. SV40 has three early proteins, the large tumor antigen, the small tumor antigen, and a small protein called 17kT that shares most of its sequence with the N-terminus of LTag. Of these, LTag is primarily responsible for cellular transformation. STag alone cannot transform cells, but improves the efficiency with which LTag performs this function. LTag's transforming effect can largely be attributed to its ability to bind the retinoblastoma protein (Rb) and the tumor suppressor protein p53; abrogating either binding site renders LTag unable to transform primary cultured cells. In fact, p53 - now established as a key driver in carcinogenesis - was originally discovered by its ability to bind LTag. Murine polyomavirus Murine polyomavirus (MPyV), described in the 1950s, was the first polyomavirus discovered and can cause tumors in rodents. MPyV has three early proteins; in addition to LTag and STag it also expresses middle tumor antigen, which is primarily responsible for the virus's transforming activity. Merkel cell polyomavirus Merkel cell polyomavirus (MCPyV), also known as Human polyomavirus 5, naturally infects humans and is associated with Merkel cell carcinoma (MCC), a rare form of skin cancer originating from Merkel cells. Although MCPyV infection is common and usually asymptomatic, a large majority of MCC tumors possess a genomically integrated copy of the