Our research focus is the deregulation of protein turnover as a central driver of tumourigenesis. This hypothesis is based on the observation that several E3 ubiquitin ligases are mutated or lost in a high proportion of human tumours and exert their function by regulating the protein stability of essential transcription factors, which also function as potent proto-oncogenes, like MYC, JUN, NICD1, CCNE1 and p63/∆Np63. By combining in vitro with in vivo models we try to understand the consequences of loss/mutation of key-components of the ubiquitin machinery and ways to counteract protein stability deregulation.
Cremona, C.A., Sancho, R., Diefenbacher, M.E., and Behrens, A. (2015). Fbw7 and its counteracting forces in stem cells and cancer: Oncoproteins in the balance. Seminars in cancer biology.
Chakraborty, A., Diefenbacher, M.E., Mylona, A., Kassel, O., and Behrens, A. (2015). The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling. Nature communications 6, 6782.
Diefenbacher, M.E., Chakraborty, A., Blake, S.M., Mitter, R., Popov, N., Eilers, M., and Behrens, A. (2015). Usp28 counteracts Fbw7 in intestinal homeostasis and cancer. Cancer research 75, 1181-1186.
Diefenbacher, M.E., Popov, N., Blake, S.M., Schulein-Volk, C., Nye, E., Spencer-Dene, B., Jaenicke, L.A., Eilers, M., and Behrens, A. (2014). The deubiquitinase USP28 controls intestinal homeostasis and promotes colorectal cancer. The Journal of clinical investigation 124, 3407-3418.
Schulein-Volk, C., Wolf, E., Zhu, J., Xu, W., Taranets, L., Hellmann, A., Janicke, L.A., Diefenbacher, M.E., Behrens, A., Eilers, M., et al. (2014). Dual regulation of Fbw7 function and oncogenic transformation by Usp28. Cell reports 9, 1099-1109.