Interaction of SV40 large T antigen with components of the nucleo/cytoskeleton

The SV40 large T antigen is a viral oncoprotein which performs multiple interactions with cellular factors to achieve a proliferative state required for viral replication as well as for transformation. The major targets in this scenario are members of the Rb family, pRb, p107. and p130, and tumor suppressor protein p53, These interactions of large T with Rb proteins and p53 are required but not sufficient for transformation. To search for unknown interaction partners of large T that might participate in its transforming activity we employed the yeast two-hybrid system. Screening a cDNA library from a large T-induced brain tumor cell line revealed a total of 86 positive clones representing 37 individual clones. Of these, four clones were selected for further analyses. Interestingly, the cDNA inserts of these clones coded for different components of the cytoskeleton, lamin C, laminin gamma1, thymosin beta4, and gelsolin. Complex formation between large T and these proteins was confirmed in vitro. Interaction of large T with these components might influence activities such as intracellular transport, signal transduction, adhesion, or migration.