Molecular basis of gene deregulation by the oncogenic transcription factor E2A-PBX1
The E2A gene is also involved in a chromosomal translocation that results in the oncogenic transcription factor E2A-PBX1. The two activation domains of E2 (AD1 and AD2) display redundant, independent, and cooperative functions in a cell-dependent manner, at least in part through an interaction with the transcriptional co-activator CBP/p300. The E2A-PBX1:CBP/p300 interaction is critical for oncogenesis. However, a molecular understanding of this interaction and associated function has been lacking. Here, we describe our use of structural biology, biophysical and biochemical approaches, and complementary cell-based assays and mouse studies to characterize the interactions of E2A-PBX1 with CBP/p300, and our ability to disrupt this interaction by an engineered peptide. Our studies are defining the molecular basis for transcriptional activation and oncogenesis by E2A and E2A-PBX1, and serve as a structural foundation for inhibitor design.
11:30-12:30 BioSci Rm. 3110