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Projekt Druckansicht

Charakterisierung der Chromatin-Remodeling Aktivität des Transkriptionsfaktors c-Myb

Fachliche Zuordnung Allgemeine Genetik und funktionelle Genomforschung
Evolutionäre Zell- und Entwicklungsbiologie der Tiere
Förderung Förderung von 2013 bis 2018
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 246701844
 
Erstellungsjahr 2017

Zusammenfassung der Projektergebnisse

Myb is an oncogenic transcription factor that plays a key role in the hematopoietic system as a regulator of cell proliferation, differentiation and survival. In previous work we have identified a highly conserved region within the Myb transactivation domain that plays a crucial role in chromatin remodelling by Myb. In this project we have studied the interaction and functional consequences of proteins interacting with the chromatin remodelling domain. Our work demonstrates that this region mediates Myb-Myb self-interactions as well as interactions with TIP60, PRMT4 and Menin. We have shown that Myb self-interaction and binding of Tip60 interferes with the interaction between Myb and the co-activator p300, whose binding site is juxtaposed to the hydrophobic region, leading to inhibition of the activity of Myb. Interestingly, replacement of two valine residues by isoleucines strongly stimulates the interactions. In the second part of the project we have focused on small molecule inhibitors of Myb and their effects on protein-protein interactions mediated by the Myb transactivation domain, including the hydrophobic region. We have successfully identified several low-molecular weight compounds as inhibitors of Myb activity, thereby demonstrating for the first time that targeting of Myb by small molecule inhibitors is feasible. However, so far all the compounds that have been studied in sufficient detail act via inhibition of the interaction of Myb with p300.

Projektbezogene Publikationen (Auswahl)

 
 

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