BK VIRUS LARGE T-ANTIGEN - INTERACTIONS WITH THE RETINOBLASTOMA FAMILY OF TUMOR-SUPPRESSOR PROTEINS AND ON CELLULAR GROWTH-CONTROL

BK virus (BKV) is a polyomavirus which infects a large percentage of t he human population, It is a potent transforming agent and is tumorige nic in rodents. BKV DNA has also been found in human brain, pancreatic islet, and urinary tract tumors, implicating this virus in neoplastic processes. BKV T antigen (TAg) is highly homologous to simian virus 4 0 TAg, particularly in regions required for mitogenic stimulation and binding to tumor suppressor proteins, The experiments presented in thi s report show that BKV TAg can bind the tumor suppressor protein p53. BKV TAg also has the ability to bind to members of the retinoblastoma (pRb) family of tumor suppressor proteins both in vivo and in vitro. H owever, these interactions are detected only when large amounts of tot al protein are used, because the levels of BKV TAg normally produced f rom viral promoter-enhancer elements are too low to bind a significant amount of the pRb family proteins in the tell, The low levels of BKV TAg produced by the viral promoter elements are sufficient to affect t he levels and the phosphorylation patterns of these proteins and to in duce serum-independent growth in these cells. Additional events, howev er, are required for full transformation. These data further support t he notion that BKV TAg can affect cellular growth control mechanisms a nd may in fact be involved in neoplastic processes.