Protein interactions play an important role in transformation by DNA tumor viruses. They might result either in activation of proto-oncogenes or, as recently suggested, in inactivation of anti-oncogenes. Polyoma medium T antigen, the principal transforming protein of polyoma, binds to the pro-oncogenes pp60c-src and pp62c-yes, thereby increasing their protein-tyrosine kinase activity. Medium T also binds to two cellular proteins of 61,000 and 37,000 daltons (61K and 37K proteins), and genetic evidence indicates that these proteins are involved in transformation. It is possible that they represent anti-oncogenes. A large fraction of the cDNA encoding the 61K protein has been sequenced, and it appears that it belongs to a new family of proteins. The goals of this proposal are (1) to purify the 37K protein and to clone and sequence its corresponding cDNA, in addition to finishing sequencing of the 61K protein cDNA; (2) to produce large quantities of the 61K and 37K proteins; (3) to prepare polyclonal and monoclonal antibodies against the 61K and 37K proteins; (4) to study their expression in the cell cycle, in different organs and during development; (5) to study the in vitro complex formation between the 61K/337K proteins and mT antigen; (6) to microinject antibodies against the 61K/37K proteins to test the effect of blocking complex formation in vivo on the biology of the cell.