The long term goal of this work is to understand the transcriptional mechanisms that underlie B lymphocyte identity. Specifically, the investigator will characterize the E2A proteins (E12 and E47) by identifying the cause of their activation in B cells and by exploring the consequences of that activation. Initially identified as Ig enhancer-binding proteins, the E2A proteins are known to be necessary for early B cell development and, hence, must be important for activating additional genes. Activity of the E2A proteins is regulated. For example protein is present in a wide variety of cells, but the ability to bind DNA as homodimers is B-cell specific. The PI's group has shown that regulation of DNA binding is a consequence of cell-specific phosphorylation and that DNA binding is not the only regulated target. There are four specific aims: 1) to continue their analysis of E47 phosphorylation, 2) to elucidate the mechanism of E47 activation by Ras, 3) to identify novel proteins that interact with E47 functionally or physically and 4) to identify novel E47-induced genes.
| Zhao, Fang; McCarrick-Walmsley, Ruth; Akerblad, Peter et al. (2003) Inhibition of p300/CBP by early B-cell factor. Mol Cell Biol 23:3837-46 |
