Evidence that SV40 surface tumor antigen originates from the nucleus and cytoplasm

Simian virus 40 large T antigen exposed at the cell surface is oligomerized and phosphorylated in a mature fashion. NP40-soluble surface T antigen, prepared from infected cells, sediments mainly as a tetramer and has a nuclear phosphorylation pattern. Since these are modifications that occur over several hours, surface T appears to be a population of older molecules. This is in apparent contradiction to kinetic studies showing that T antigen arrives at the surface in 20 min. We present a model to account for this apparent discrepancy. It postulates that both newly-synthesized and older, mature molecules are transported to the surface. The newly-synthesized molecules are highly unstable and lost rapidly from the surface whereas the mature molecules are stable and accumulate over time. This stability may be due to oligomerization and/or phosphorylation or to an interaction with other surface molecules that act as anchors. Our model further proposes that most of the T antigen in transit to the surface is newly-synthesized protein from the cytoplasm, while the majority of the T antigen at the surface is mature protein from the nucleus.