PDZ proteins

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

  1. 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).
  2. 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
  3. 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).
  4. 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).
  5. 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).
  6. 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).
  7. Ress, A. and Moelling, K. Bcr is a negative regulator of the Wnt signalling pathway. EMBO reports 6, 11, 1095-1100 (2005) – Ress 2005
  8. Ress, A. and Moelling, K. Interaction partners of the PDZ domain of Erbin. Protein & Peptide Letters 13, 877-881 (2006).
  9. Ress, A. and Moelling, K. Bcr interferes with β-catenin-Tcf1 interaction FEBS Letters 580, 1227-1230 (2006).
  10. 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
  11. 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).
  12. 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
  13. 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).
  14. 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
  15. 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).
  16. 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
  17. Ress, A., Radziwill, G. and Moelling, K. The PDZ-protein Erbin modulates β-catenin-dependent transcription Eur Surg Res. 41 (3), 284-289 (2008).
  18. 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
  19. 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)