Universität zu Köln 

Prof. Dr. Manolis Pasparakis

Institut für Genetik/CECAD Forschungszentrum
Universität zu Köln
email: pasparakis@uni-koeln.de
phone: +49-(0)221 470 1526
website

Running time: 2007 – 2011

Abstract

The NF-?B signalling pathway regulates cellular responses to infection, inflammation and stress and is implicated in the pathogenesis of many human diseases. The I?B kinase (IKK) complex is essential for NF-?B activation, however the molecular interactions regulating IKK function are poorly understood. In this project we aim to elucidate the posttranslational mechanisms controlling IKK function. Using an in vivo proteomics approach, by generating knock-in mice expressing TAP-tagged IKK subunits, we aim to identify proteins that interact with IKK subunits and regulate their activity in a tissue- and/or stimulus-specific manner.

(A final report will follow.)

Publications related to the project:

Vereecke, L., Sze, M., Guire, C.M., Rogiers, B., Chu, Y., Schmidt-Supprian, M., Pasparakis, M., Beyaert, R., and van Loo, G. (2010). Enterocyte-specific A20 deficiency sensitizes to tumor necrosis factor-induced toxicity and experimental colitis. J. Exp. Med. 207, 1513-1523.

Schramek, D., Leibbrandt, A., Sigl, V., Kenner, L., Pospisilik, J.A., Lee, H.J., Hanada, R., Joshi, P.A., Aliprantis, A., Glimcher, L., Pasparakis, M., Khokha, R., Ormandy, C.J., Widschwendter M., Schett, G., and Penninger, J.M. (2010). Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 468, 98-102.

Pasparakis, M. (2009). Regulation of tissue homeostasis by NF-kappaB signalling: implications for inflammatory diseases. Nat. Rev. Immunol. 9, 778-788. (review)

Michallet, M.C., Meylan, E., Ermolaeva, M.A., Vazquez, J., Rebsamen, M., Curran, J., Poeck, H., Bscheider, M., Hartmann, G., Konig, M., Kalinke, U., Pasparakis, M., and Tschopp, J. (2008). TRADD protein is an essential component of the RIG-like helicase antiviral pathway. Immunity 28, 651-661.

Luedde, T., Heinrichsdorff, J., de Lorenzi, R., De Vos, R., Roskams, T., and Pasparakis, M. (2008). IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver. Proc. Natl. Acad. Sci. U S A 105, 9733-9738.

Gareus, R., Kotsaki, E., Xanthoulea, S., van der Made, I., Gijbels, M.J., Kardakaris, R., Polykratis, A., Kollias, G., de Winther, M.P., and Pasparakis, M. (2008). Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis. Cell Metab. 8, 372-383.

Ermolaeva, M.A., Michallet, M.C., Papadopoulou, N., Utermohlen, O., Kranidioti, K., Kollias, G., Tschopp, J., and Pasparakis, M. (2008). Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat. Immunol. 9, 1037-1046.