Role of RELNFkB members in v-rel induced transformation

The REV-T virus is the most virulent of all the known acutely transforming retroviruses. The transforming activity of the virus resides within the virally encoded v-rel oncogene, the first member identified of a growing number of transcriptional regulators called the REL/NF$ kappa$B family. The mechanism of v-rel mediated transformation of avian as well as mammalian cells remains elusive, however immunoprecipitations performed with anti-v-rel antibodies clearly reveal associated proteins which include pp40 I$ kappa$B alpha, p68 c-rel, hsc70 and the p124 and p115 precursors for the p50 and p52 subunits of the REL/NF$ kappa$B family, respectively. In normal cells these same proteins are also found associated with the proto-oncogene c-rel. REL/NF$ kappa$B members have been implicated in the regulation of lymphocyte growth, differentiation and activation suggesting that v-rel mediated transformation involves the deregulation of normal REL/NF$ kappa$B function. In order to better understand v-rel protein function, we have investigated several gene regulatory systems. Specifically, we have tested and used phophorothioate oligonucleotides as well as vectors producing antisense RNA for the purpose of disrupting gene expression in avian cells. We have tested the RCAS system (Replication competent avian leukosis LTR & splice acceptor) of vectors to infect and disseminate within a chicken effectively producing somatically transgenic chickens where cloned genes may be expressed from the infected cells. Also investigated was the feasability of using the tetracycline regulated gene expression system in avian cells. These new regulatory systems will allow us to understand the role played by individual members of the REL/NF$ kappa$B family in cellular transformation