Figure 1.

FoxM1 expression is repressed by FoxO3a. FoxO3a may repress FoxM1 expression in one of three ways, which may not be mutually exclusive. First, FoxO3a may bind to a Fox consensus site at position −88 of the FoxM1 promoter. This could lead to FoxM1 repression. Second, expression of the Myc antagonists Mad and Mxi1 are driven by FoxO3a. Mad and Mxi1 compete with Myc to dimerize with Max. The Max/Myc dimer binds to E-boxes (CACTGT) located within the FoxM1 promoter to drive FoxM1 expression, while Mad/Max and Mxi1/Max dimers bind the same E-boxes, but repress expression. Thus, increased expression of Mxi1 and Mad by FoxO3a could inhibit FoxM1 expression by blocking Myc/Max dimerization. Third, Myc protein levels decrease when FoxO3a expression is increased, perhaps through a post-translational mechanism, providing another method to potentially repress FoxM1 expression following FoxO3a activation. This figure is based on work from Delpuech et al. (2007) and Fernandez et al. (2003).