Role of serine/threonine protein phosphatase 2A in cancer

The serine/threonine protein phosphatase 2A (PP2A) appears to be critically involved in cellular growth control and potentially in the development of cancer. A few studies indicated that this enzyme might actually exert tumor suppressive function. However, other findings demonstrated the requirement for PP2A in cell growth and survival, which is not a characteristic of a t ypical tumor suppressor. This apparent discrepancy might be due to the fact that PP2A is a multitask enzyme system, rather than a single enzyme. Its i ndividual subunits are encoded by a heterogeneous group of genes which give rise to a multitude of different PP2A holoenzyme complexes. Thus, the puzz ling observation that PP2A exerts inhibitory, as well as stimulatory, effec ts on cell growth could be due to the activity of different PP2A complexes with distinct subcellular location and divers substrate specificity. At the same time, this abundance of PP2A components provides a large target for m utations that might derail proper enzyme function and could contribute to t he process of tumorigenesis. So far, however, it has not been unequivocally established whether such mutations, examples of which have indeed been fou nd in human cancer cells, result in the activation of an oncogenic function or rather in the inactivation of the presumed tumor suppressive role of PP 2A. Therefore, the general opinion of PP2A as being a tumor suppressor need s to be viewed with caution. (C) 2001 Elsevier Science Ireland Ltd. All rig hts reserved.