Small tumor antigen

The small tumor antigen (also called the small T-antigen and abbreviated STag or ST) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. STag is expressed early in the infectious cycle and is usually not essential for viral proliferation, though in most polyomaviruses it does improve replication efficiency. The STag protein is expressed from a gene that overlaps the large tumor antigen (LTag) such that the two proteins share an N-terminal DnaJ-like domain but have distinct C-terminal regions. STag is known to interact with host cell proteins, most notably protein phosphatase 2A (PP2A), and may activate the expression of cellular proteins associated with the cell cycle transition to S phase. In some polyomaviruses - such as the well-studied SV40, which natively infects monkeys - STag is unable to induce neoplastic transformation in the host cell on its own, but its presence may increase the transforming efficiency of LTag. In other polyomaviruses, such as Merkel cell polyomavirus, which causes Merkel cell carcinoma in humans, STag appears to be important for replication and to be an oncoprotein in its own right. The genes for both the small and the large tumor antigen are encoded in the "early region" of the polyomavirus genome, so named because this region of the genome is expressed early in the infectious process. (The "late region" contains genes encoding the viral capsid proteins.) The early region typically contains at least two genes and is 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 STag (and sometimes other tumor antigens as well, such as the murine polyomavirus middle tumor antigen). Polyomavirus STag proteins are usually around 170-200 residues long and consist of two distinct regions as a result of this genetic encoding. STag and LTag share a common N-terminal domain called the J domain, which is around 80-90 residues long, has homology to DnaJ proteins, and functions as a molecular chaperone.