Loss or inhibition of the
serine/
threonine protein phosphatase 2A (PP2A) has revealed a critical
tumor suppressor function for PP2A. However, PP2A has also been shown to have important roles in cell cycle progression and survival. Therefore, PP2A is not a typical
tumor suppressor. This is most likely due to the fact that PP2A represents a large number of different
holoenzymes. Further understanding of PP2A function(s), and especially its
tumor suppressor activity, will depend largely on our ability to determine specific targets for these different PP2A
holoenzymes and to gain an understanding of how these targets confer
tumor suppressor activity or contribute to cell cycle progression and cell survival. Recent work has identified c-Myc as a target of the PP2A
holoenzyme, PP2A-B56alpha. This
holoenzyme also negatively regulates
beta-catenin expression and modulates the anti-apoptotic activity of Bcl2, thus characterizing PP2A-B56alpha as a
tumor suppressor PP2A
holoenzyme. This review will focus on the role of PP2A-B56alpha in regulating c-Myc and will place this
tumor suppressor activity of PP2A within the context of its other
tumor suppressor functions. Finally, the mechanism(s) through which PP2A-B56alpha
tumor suppressor activity may be lost in
cancer will be discussed.