Protein phosphatase 2A complex (PP2A)

Protein phosphatase 2A complex (PP2A) is a highly conserved, ubiquitously expressed serine/threonine phosphatase that exists as a multi-subunit enzyme complex, most commonly formed by a catalytic (C), a structural/scaffold (A), and a regulatory (B) subunit, each with several isoforms and families, generating extensive combinatorial diversity and tissue-specific functions[1][2][4][6]. PP2A dephosphorylates a wide range of critical signaling proteins, such as Akt, p53, c-Myc, and β-catenin, and is an essential regulator of cellular processes including signal transduction, cell cycle progression, cell proliferation, apoptosis, and maintenance of cell adhesion and polarity[1][4][5]. PP2A has a well-established role as a tumor suppressor, with somatic mutations, epigenetic silencing, or post-translational modifications of its subunits contributing to carcinogenesis and disease[1][4][6]. PP2A complexes are implicated in diverse human diseases including cancer, neurodegenerative disorders, and cardiovascular diseases, often depending on the specific subunit composition and tissue expression[1][4]. Pharmacological modulators of PP2A, such as okadaic acid and experimental drugs like LB-100, are used in research and early clinical investigation; selective targeting remains difficult due to the complex’s structural and functional diversity[1][4][5]. Biomarkers for altered PP2A function include subunit gene mutations found in certain cancers and neurodevelopmental syndromes, and altered activity or expression in tumors[1][4][6]. Safety concerns with therapeutic targeting of PP2A stem from its ubiquitous, indispensable role in normal cellular regulation, making subunit- or isoform-specific approaches a major focus for future drug development[1][4].

Other names

Protein phosphatase 2APP2A holoenzymeserine/threonine-protein phosphatase 2A

Inhibition leads to increased phosphorylation of substrates regulating proliferation, apoptosis, and cell cycle Modulation can restore tumor suppressor activity in cancer through normalization of phosphatase function