Protein phosphatase 2A holoenzyme (PP2A)

Protein phosphatase 2A (PP2A) is a major, ubiquitous serine/threonine phosphatase that functions as a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and a diverse array of regulatory B subunits (UniProt, 2023). It plays a critical role in cellular homeostasis by counteracting the activity of protein kinases in signaling pathways such as MAPK/ERK, PI3K/AKT, and Wnt (PubMed, 2021). In many cancers, PP2A activity is suppressed through mutations in its subunits or the overexpression of endogenous inhibitors like SET and CIP2A, leading to uncontrolled cell proliferation and survival (NIH, 2022). Consequently, PP2A is a significant therapeutic target, with research focusing on Small Molecule Activators of PP2A (SMAPs) to restore its tumor-suppressive function (Nature Reviews Drug Discovery, 2020). Conversely, PP2A inhibitors like LB-100 are being investigated in clinical trials to enhance the efficacy of chemotherapy and radiation by preventing the repair of DNA damage in tumor cells (ClinicalTrials.gov, 2023). Beyond oncology, PP2A dysfunction is linked to neurodegenerative diseases, particularly Alzheimer's, where its reduced activity contributes to the hyperphosphorylation of Tau protein (PubMed, 2019).

Other names

Protein phosphatase 2PPP2Serine/threonine-protein phosphatase 2APP2A complexPhosphoprotein phosphatase 2A

Dephosphorylation of serine and threonine residues on target proteins to modulate signaling pathways; therapeutic strategies involve either the activation of the holoenzyme to restore tumor suppressive functions or its inhibition to sensitize cancer cells to DNA-damaging therapies.