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Novel approaches towards understanding of gene transcription using small molecules as tools (DEKKER40)
Start date: Sep 3, 2007, End date: Sep 2, 2010 PROJECT  FINISHED 

"Small molecule modulators of protein function proved to be effective tools to elucidate the functions of newly identified proteins in reverse chemical genetic studies. In the field of gene transcription regulation many new proteins with a poorly defined function are being discovered. Among these proteins many enzymes are found that modulate acylation and phosphorylation. These posttranslational modifications play an important role in cellular localization and protein-protein interactions of transcription factors. An interesting feature is that acylation competes with other posttranslational modification such as ubiquitinylation, sumoylation, palmitoylation etc. Acetylation can thus be considered a key regulatory event. We propose to develop small molecule inhibitors to study lysine acetyl transferases in a reverse chemical genetics approach. Furthermore, we propose to develop innovative chemical cross-linkers to specifically cross link lysine acetyl transferases and their targets in vivo in order to elucidate the binding partners of these enzymes. Together these small molecules will provide tools to study spatial and temporal control in gene transcription by the Smad transcription factors in fluorescence microscopy studies of cell based systems"

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