NOVEL MECHANISMS OF E2F INDUCTION BY BK VIRUS LARGE-T ANTIGEN - REQUIREMENT OF BOTH THE PRB-BINDING AND THE J-DOMAIN

E2F activity is regulated in part by the retinoblastoma family of tumo r suppressor proteins. Viral oncoproteins, such as simian virus 40 (SV 40) large-T antigen (TAg), adenovirus E1A, and human papillomavirus E7 , can disrupt the regulation of cellular proliferation by binding to p Rb family members and dissociating E2F-pRb family protein complexes, B K virus (BKV), which infects a large percentage of the human populatio n and has been associated with a variety of human tumors, encodes a TA g homologous to SV40 TAg. It has been shown that BKV TAg, when express ed at low levels, does not detectably bind to pRb family members, yet it induces a serum-independent phenotype and causes a decrease in the overall levels of pRb family proteins. The experiments presented in th is report show that, despite the lack of TAg-pRb interactions, BKV TAg can induce transcriptionally active E2F and that this induction does in fact require an intact pRb-binding domain as well as an intact J do main. In addition, E2F-pRb family member complexes can be detected in both BKV and SV40 TAg-expressing cells. These results suggest the pres ence of alternate cellular mechanisms for the release of E2F in additi on to the well-established model for TAg-pRb interactions. These resul ts also emphasize a role for BKV TAg in the deregulation of cellular p roliferation, which may ultimately contribute to neoplasia.