PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer

Abstract PP2A is a highly conserved eukaryotic serine/threonine protein phosphatase of the PPP family of phosphatases with fundamental cellular functions. In cells, PP2A targets specific subcellular locations and substrates by forming heterotrimeric holoenzymes, where a core dimer consisting of scaffold (A) and catalytic (C) subunits complexes with one of many B regulatory subunits. PP2A plays a key role in positively and negatively regulating a myriad of cellular processes, as it targets a very sizable fraction of the cellular substrates phosphorylated on Ser/Thr residues. This review focuses on insights made toward the understanding on how the subunit composition and structure of PP2A holoenzymes mediates substrate specificity, the role of substrate modulation in the signaling of cellular division, growth, and differentiation, and its deregulation in cancer.