The Tal1 oncogene is a class II basic helix-loop-helix (bHLH) transcription 
factor, overexpressed in as much as 60% of T cell acute lymphoblastic leukemia 
cases. Like other class II bHLH proteins, Tal1 can heterodimerize with the class 
I bHLH proteins, such as E47, and bind to a DNA recognition sequence termed E 
box. Therefore, it is believed that the oncogenic capacity of Tal1 lies in its 
ability, as a heterodimer with E47, to activate aberrantly a set of 
"leukemogenic" genes in T cells. However, compared with E47 homodimers, Tal1/E47 
heterodimers are very poor transactivators. Thus the effect of Tal1 is actually 
to inhibit E47 homodimer activity. Here we propose that the transforming 
properties of Tal1 are the result of its ability to inhibit E47 activity. We 
address the mechanism of Tal1 inhibition and demonstrate that Tal1/E47 
heterodimers cannot activate transcription because their respective activation 
domains are incompatible. Furthermore, we present data showing that Tal1 can 
inhibit E47-mediated activation of the CIP1 gene. Finally, we demonstrate that 
Tal1 inhibits E47 activity in leukemic T cells.