Predictive Modeling of CDC25 Isoforms for Dual-action Phosphatase Substrate Specificity

Abstract

Cancer is caused by a dysfunctional cell cycle that allows for excess cell division. The cell cycle is regulated by a series of kinases and phosphatases. Phosphatases are important proteins that remove phosphate groups from other proteins to induce a cellular response. CDC25 phosphatase and its isoforms, in particular, are phosphatases that play a key regulatory role in cell proliferation. However, research has shown that these phosphatases can play both an oncogenic and tumor suppressive function depending on the substrate that it is acting upon. This paper analyzes predictive protein interaction models between CDC25 isoforms and an oncogenic substrate, CDK1, and between a tumor suppressive substrate, CHEK2, to find hot spot residues which may have a role in substrate specificity. Identifying these interactions would identify potential targets for cancer therapies that could manipulate CDC25 phosphatases to exhibit tumor suppressive activity and while inhibiting its oncogenic activity.