We are interested in the gene regulation in response to RTK cascades. Specifically ETS  genes and the ras/erk pathway in normal and tumor development.  The last few years we have focused our efforts on Erf a transcription factor of the ets-oncogene family.In contrast to the other ets genes is a transcriptional repressor and can act as a tumor suppressor. We studied the mechanism of its regulation by Erks, and established that a unique protein interaction determines its phosphorylation. We determined that this phosphorylation leads to its regulation as a transcription factor by determining its sub-cellular compartmentalisation. We studied its function as a tumor suppressor and we established that Erf can repress cell proliferation via an Rb-dependent pathway and that specific non Erk-regulated mutations can be effective against ras-induced tumorigenesis. We also studied its function in the context of the whole animal and found that the loss of Erf leads to embryonic lethality as a result of extensive proliferation and defective differentiation of the trophoblast stem cell. Recently we are focusing on the role of Erf in breast epithelial-to -mesenchymal-transition (EMT) as well as its possible role in neural development.

Papadaki, C., Alexiou, M., Cecena, G., Verykokakis, M., Bilitou, A., Cross, J. C., Oshima, R. G., and Mavrothalassitis, G. (2005) Transcriptional repressor erf determines extraembryonic ectoderm differentiation.  Mol Cell Biol 27: 5201-5213.

Le Gallic L; Virgilio L; Cohen P; Biteau B; Mavrothalassitis G (2004) ERF nuclear shuttling, a continuous monitor of Erk activity that links it to cell cycle progression. Mol. Cell. Biol. 24: 1206-1218.

Lionel Le Gallic, Dionyssios Sgouras,  Gregory Beal Jr  and George Mavrothalassitis. (1999) The transcriptional repressor ERF, is a ras/MAPK target that regulates cellular proliferation. Mol. Cell. Biol. 19: 4121-4133.

Sgouras, D. N., Athanasiou, M. A., Beal, G. J., Fisher, R. J., Blair, D. G. and Mavrothalassitis, G. J.: ERF (1995) An ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis and regulated by phosphorylation during cell cycle and mitogenic stimulation. EMBO J. 14: 4781-4793.

Mavrothalassitis, G. J., Watson, D. K. and Papas, T. S. (1990)   Molecular and functional characterization of the promoter of ETS2, the human c-ets-2 gene. Proc. Natl. Acad. Sci. USA 87: 1047-1051.