Cell Transformation
The Cell Transformation Group is internationally recognized as a leading laboratory in the study of virally encoded oncogenes. In the past few years we have identified many of the polyoma virus middle T-antigen binding proteins, and proven that the interactions mimic those occurring during receptor signalling. This has enabled us to use middle T-antigen not only to identify proteins involved in tumorigenesis, but also as a probe in determining how signal transduction pathways function in both normal and abnormal conditions. This approach is producing important new information that will have a significant impact on the identification of new targets for anti-tumour therapy. Our future plan is to expand this methodology over the next few years and apply the knowledge gained from examining middle T-antigen to the study of human cancers. New projects planned include establishing FRET based imaging techniques in collaboration with other signalling groups in the Faculty, generating structural information on signalling molecules through collaboration with the BBSRC Centre for Structural Biology at South Kensington, and using our expertise in signalling mechanisms to develop translational approaches using targeted antibodies for diagnosis, and identifying new therapeutic molecules.
The MT complex
MT is represented linearly, and the sites involved in binding cellular proteins shown above and below. Hsc 70 is heat shock cognate protein 70, PP2A protein phosphatase 2A, pp60c-src represent c-SRC, PI3K phosphatidylinositol 3 kinase and PLCg-1 phospholipase Cg-1.
Funding
Biotechnology and Biological Science Research Council, Association for International Cancer Research, OSTC Belgium.
Selected publications
Dilworth, S.M. (2002). Polyoma virus middle T antigen and its role in identifying cancer-related molecules. Nat. Rev. Cancer, 951-956o:p
Nicholson, P.R., Empereur, S., Glover, H.R., and Dilworth, S.M. (2001). ShcA tyrosine phosphorylation sites can replace ShcA binding in signalling by middle T-antigen. EMBO J. 20 6337-6346.
Ichaso, N., and Dilworth, S.M. (2001). Cell transformation by the middle T-antigen of polyoma virus. Oncogene 20 7908-7916.
Glover, H.R., Brewster, C.E.P., and Dilworth, S.M. (1999). Association Between src-kinases and the Polyoma Virus Oncogene Middle T-antigen Requires PP2A and a Specific Sequence Motif. Oncogene. 18 4364-4370.
Brewster, C.E.P., Glover, H.R., and Dilworth, S.M. (1997). Pp60c-src Binding to Polyomavirus Middle T-Antigen (MT) Requires Residues 185 to 210 of the MT Sequence. J. Virol. 71 5512-5520.
Dilworth, S.M. (1995). Polyoma virus middle T antigen: meddler or mimic? Trends in Microbiology. 3 31-35.
Dilworth, S.M., Brewster, E.P., Jones, M.D., Lanfrancone, L., Pelicci, G., and Pelicci, P.G. (1994). Transformation by polyoma virus middle T-antigen requires the binding and tyrosine phosphorylation of Shc. Nature 367 87-90.
