PDZ domains are present in proteins which turned out to be tumor suppressor proteins. This was unexpected and the result of a BMBF project planned to analyze the opposite. Thus inhibition of PDZ binding is not a potential anti-cancer approach, but can lead to metastasis as shown for Src.
for further links to publications see Oncogenes and Cancer
Publications about PDZ proteins
- Buchert, M., Schneider, S., Adams, M., Baechi, T., Moelling, K. and Hovens, C.M.: The junction-associated protein AF-6 interacts and clusters with specific Eph receptor tyrosine kinase at specialized sites of cell-cell-contact in the brain. J. Cell Biol 144, 361-371 (1999).
- Schneider, S., Buchert, M., Adams, M., Baechi, T., Moelling, K. and Hovens, C.M.: Mutagenesis and selection of PDZ domains able to bind to new protein targets. Nature Biotechnology 17, 170-175 (1999) – Schneider 1999
- Radziwill, G., Erdmann, R.A., Margelisch, U., Moelling K. The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain. Molecular and Cellular Biology 23, 13, 4663-4672 (2003).
- Boisguerin, P., Leben. R., Ay. B., Radziwill G., Moelling K., Dong, L., Volkmer-Engert R.: An Improved Method for the Synthesis of Cellulose Membrane-Bound Peptides with Free C Termini is Useful for PDZ Domain Binding Studies Chemistry & Biology 11, 449-459 (2004).
- Wiedemann, U., Boisguerin, P., Leben, R., Leitner, D., Krause, G., Moelling K., Volkmer-Engert R. and Oschkinat H. Quantification of PDZ domain specificity, prediction of ligand affinity and rational design of super-binding peptides. J. Mol. Biol., 343, 703-718 (2004).
- Ziogas, A., Moelling, K., Radziwill, G. CNK1 is a scaffold protein that regulates Src-mediated Raf-1 activation. J Biol Chem. 280, 25, 24205-24211 (2005).
- Ress, A. and Moelling, K. Bcr is a negative regulator of the Wnt signalling pathway. EMBO reports 6, 11, 1095-1100 (2005) – Ress 2005
- Ress, A. and Moelling, K. Interaction partners of the PDZ domain of Erbin. Protein & Peptide Letters 13, 877-881 (2006).
- Ress, A. and Moelling, K. Bcr interferes with β-catenin-Tcf1 interaction FEBS Letters 580, 1227-1230 (2006).
- Lorger, M. and Moelling, K. Regulation of epithelial wound closure and cell-cell adhesion by interaction of AF6 with actin cytoskeleton. J Cell Scences 119, 3385-3398 (2006) – Lorger 2006
- Joshi, M., Vargas, C., Moelling, K., Boisguerin, P., Diehl, A., Krause, G., Schmieder, P., Hagen, V., Schade, M., Oschkinat, H. Discovery of low-molecular-weight ligands for the AF6PDZ domain. Angew. Chem. Int. Ed. 45, 3790-3795 (2006).
- Radziwill, G., Weiss, A., Heinrich, J., Baumgartner, M., Boisguerin, P., Owada, K., Moelling, K. Regulation of c-Src by binding to the PDZ domain of AF-6. EMBO J, 26, 2633-2644 (2007) – Radziwill 2007
- Keyser, J., Lorger, M., Pavlovic, J., Radziwill, G. and Moelling, K. Role of AF6 protein in cell-to-cell spread of Herpes simplex virus 1. FEBS Letters 581, 5349-5354 (2007).
- Weiss, A., Baumgartner, M., Radziwill, G. Dennler, J. and Moelling, K. c-Src is a PDZ-interacting partner and substrate of the E3 ubiquitin ligase ligand-of-numb protein X1. FEBS Lett. 581, 5131-5136 (2007) – Weiss 2007
- Boisguerin, P., Ay, B., Radziwill, G., Fritz, R.D., Moelling, K. and Volkmer, R. Characterization of a Putative Phosphorilation Switch: Adaption of SPOT Synthesis to analyze PDZ Domain Regulation Mechanisms ChemBioChem 8, 2302-2307 (2007).
- Baumgartner, M., Radziwill, G. Lorger, M., Weiss, A. and Moelling, K. c-Src-mediated epithelial cell migration and invasion regulated by PDZ binding site. Molecular and Cellular Biology, 28, 642-655 (2008) – Baumgartner 2008
- Ress, A., Radziwill, G. and Moelling, K. The PDZ-protein Erbin modulates β-catenin-dependent transcription Eur Surg Res. 41 (3), 284-289 (2008).
- Baumgartner, M., Weiss, A., Fritzius, T., Heinrich, J., and Moelling, K. (2009). The PDZ protein MPP2 interacts with c-Src in epithelial cells. Experimental Cell Research 315, 2888-2898 (2009) – Baumgartner 2008
- Vargas, C., Radziwil, G., Krause, G., Diehl, A., Keller, S., Schmieder, P., Doyle, D., Moelling, K., Hagen, V., Schade, M. and Oschkinat, H. (2009) Small-Molecule Inhibitors of AF6 PDZ-Mediated Protein-Protein Interactions. (in press 2010)