Protein phosphatase 2A holoenzyme containing PR55α subunit (PP2A-B55α)

The Protein Phosphatase 2A (PP2A) holoenzyme containing the PR55α (also known as B55α or PPP2R2A) regulatory subunit is a critical heterotrimeric enzyme complex that regulates a wide range of cellular processes by dephosphorylating serine and threonine residues (PMID: 32029625). This specific holoenzyme is composed of a catalytic C subunit, a structural A subunit, and the PR55α regulatory subunit, which provides substrate specificity and subcellular localization (UniProt: P67775). PP2A-B55α is a major regulator of the cell cycle, particularly during the exit from mitosis, and it modulates key signaling pathways such as PI3K/Akt, MAPK/ERK, and Wnt/β-catenin (PMID: 28242762). In many cancers, PR55α acts as a tumor suppressor and is frequently lost or downregulated, leading to the hyperactivation of oncoproteins like c-Myc and Akt (PMID: 32029625). Conversely, in certain contexts like pancreatic cancer, it may promote tumorigenesis by sustaining oncogenic signaling (PMID: 27013193). Beyond oncology, PP2A-B55α is the primary phosphatase responsible for dephosphorylating Tau protein in the brain, making its dysfunction a hallmark of Alzheimer's disease (PMID: 15155836). Therapeutic efforts focus on developing small-molecule activators (SMAPs) to restore its tumor-suppressive or neuroprotective functions, though achieving isoform specificity remains a significant challenge (PMID: 32029626).

Other names

PP2A-PR55αB55α-PP2APPP2R2A-PP2AProtein phosphatase 2A regulatory subunit B alpha holoenzymePP2A-B55alpha

Allosteric activation or stabilization of the heterotrimeric complex to restore phosphatase activity against oncogenic or pathogenic substrates such as c-Myc, Akt, and Tau (PMID: 32029625, PMID: 32029626).