-(see german version)
Project management at the University of Würzburg:
Mutations which frequently occur in colon cancer affect to main cellular functions: proliferation and cell survival. Unrestricted proliferation of apoptosis-resistant cell populations provides opportunity for the accumulation of further genetic alterations, required for the manifestation of the fully transformed phenotype. C-Raf is an essential component of proliferation and survival control. In the past mutants of C-Raf have been characterized which selectively affect one of these functions and thus should allow to delineate the contribution of specific Raf-dependent pathways to the development of apoptosis deficiency in colon cancer, which also contributes to therapy resistance. This work aims at the development of strategies to reverse apoptosis resistance. Two different approaches will be followed. For one we attempt the conditional ablation of the C-Raf protein and secondly we aim at blocking Raf-dependent signaling pathways buy using dominant negative mutants of C-Raf.
from 04.1999 to 03.2002
Sonstige Stiftung ( Scheel-Stiftung ) ,Granting date: 25.03.1999
- Afanassiev, V., J. Troppmair, M. Schuler, C. Weber, and U. R. Rapp..
(1998). Production and characterization of monoclonal antibodies against human BAD protein.. (monograph)
- Digby, M., U. Rapp, R. Götz, G. Pei, F. Metzger, L. Wixler, J. Lowenthal, D. Bowtell, J. Troppmair, and M. Sendtner..
(submitted). Expression of the IAP homologue ITA suppresses NGF- induced differentiation and TNFalpha- induced apoptosis in PC12 cells.. (monograph)
- Hagemann, C., S. Mazurek, U. Frey, J. Beigel, C. Weber, J. Troppmair, E. Eigenbrodt, and U. R. Rapp..
(submitted). A-Raf kinase and pyruvate kinase type M2 link mitogenic signaling with metabolism.. (monograph)
- Houben, R., J. Troppmair, V. Le Mellay, C. Hagemann, S. Mazurek, U. Frey, J. Beigel, C. Weber, R. Benz, E. Eigenbrodt, and U. R. Rapp..
(2001). Regulation if glycolysis by raf protein serine/threonine kinases.. (monograph)
- Jordan, B. W., D. Dinev, V. LeMellay, J. Troppmair, R. Gotz, L. Wixler, M. Sendtner, S. Ludwig, and U. R. Rapp..
(2001). Neurotrophin Receptor-interacting Mage Homologue Is an Inducible Inhibitor of Apoptosis Protein-interacting Protein That Augments Cell Death.. (monograph)
- Kerkhoff, E., L. M. Fedorov, R. Siefken, A. O. Walter, T. Papadopoulos, and U. R. Rapp..
(2000). Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein.. (monograph)
- Le Mellay, V., J. Troppmair, R. Benz, and U. R. Rapp..
(2002). Negative regulation of mitochondrial VDAC channel by Raf-1 kinase.. (monograph)
- Rapp, U. R., and J. Troppmair..
(2001). Dominant oncogenes as cancer targets: role of raf kinases and myc, two master regulators of phenotypic and genotypic stability. In Einfluss von Genomprojekt und Pharmagenetik auf die medizinische Entwicklung.. (monograph)
- Troppmair, J., and U. R. Rapp..
(2000). [Deregulation of intracellular signal pathways in colorectal carcinoma].. (monograph)
- von Gise, A., P. Lorenz, C. Wellbrock, B. Hemmings, F. Berberich-Siebelt, U. R. Rapp, and J. Troppmair..
(2001). Apoptosis suppression by Raf-1 and MEK1 requires MEK- and phosphatidylinositol 3-kinase-dependent signals.. (monograph)
- Zhong, J., J. Troppmair, and U. R. Rapp..
(2001). Independent control of cell survival by Raf-1 and. (monograph)