Expression of short peptides in vivo to modulate protein interactions

Interaction of proteins is central to various cellular processes like cell growth, proliferation, differentiation and programmed cell death. The interactions can furthermore be attributed to specified biochemical processes like transcription, translation or replication Some proteins are highly specific to interact with certain partners. They also can interact with many other proteins and even form larger multifunctional complexes. To study the specific role of a single protein-protein interaction of a multifunctional protein or protein complex, it is necessary to interrupt each single interaction individually to elucidate their respective role and influence they exert. There are many ways to interrupt protein interactions. One is expressing specific peptides in vivo to target a known protein-protein interaction. In order to accomplish this, an efficient retroviral expression vector system capable of expressing peptides was developed. To target known protein-protein interactions, peptides with sequences homolog to one of the interacting domains were expressed. As one example, peptides derived from the Ros tyrosine phosphorylation domain were expressed to target the interaction between the tyrosine kinase Ros and PTP SHP-1. In a second example peptides based on the LXXLL motif important for the interaction of transcription factors and coactivators were expressed to disrupt this interaction. Furthermore, the peptide expression system was used to establish a peptide library that can be used to screen for new peptides influencing cellular processes. ...