Protein phosphatase 2A (PP2A) holoenzyme complex (PP2A)

Protein phosphatase 2A (PP2A) is a ubiquitous and highly conserved serine/threonine phosphatase that functions as a heterotrimeric holoenzyme complex. This complex typically consists of a catalytic C subunit (PPP2C), a structural A subunit (PPP2R1), and one of several regulatory B subunits (PPP2R2-PPP2R5), which determine substrate specificity and subcellular localization (UniProt P67775, P30153). PP2A acts as a critical negative regulator of many essential signaling pathways, including the Akt, MYC, and MAPK pathways, thereby functioning as a major tumor suppressor in human cancers (PubMed: 30635554). Its activity is frequently compromised in malignancy through mutations, loss of subunits, or the upregulation of endogenous inhibitors like CIP2A and SET (NIH: PMC5660647). Consequently, therapeutic efforts focus on either activating PP2A using small-molecule activators (SMAPs) to suppress oncogenic signaling or inhibiting it with compounds like LB-100 to enhance the efficacy of DNA-damaging agents (PubMed: 28841415). Additionally, PP2A plays a vital role in neurobiology, where its downregulation is linked to Tau hyperphosphorylation in Alzheimer's disease.

Other names

Serine/threonine-protein phosphatase 2APP2A heterotrimeric complexPPP2Protein phosphatase 2PP2A-A-B-C complex

Dephosphorylation of phosphoserine and phosphothreonine residues on regulatory proteins to modulate signaling cascades such as the PI3K/Akt/mTOR, MAPK/ERK, and Wnt/beta-catenin pathways.