PPPPP2A

PPPP2A typically refers to protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in eukaryotic cells. PP2A functions as a heterotrimeric holoenzyme that dephosphorylates numerous substrates to regulate signaling pathways. The core enzyme consists of three subunits: a catalytic C subunit (PP2AC), a scaffolding A subunit (PP2AA), and a regulatory B subunit that dictates substrate specificity and localization.

The catalytic subunits are encoded by PPP2CA and PPP2CB; scaffold A subunits by PPP2R1A and PPP2R1B. The regulatory B subunits are encoded by several gene families, including PPP2R2 (B55), PPP2R5 (B56), and PPP2R3 (PR72/PR130 family). The combination of subunits determines substrate range, localization, and response to cellular cues. Post-translational modification of the catalytic subunit, such as methylation of the C-terminal leucine by LCMT1 and demethylation by PME-1, regulates holoenzyme assembly and activity.

PP2A participates in numerous cellular processes by dephosphorylating key signaling nodes such as AKT, GSK3β, CDKs, p53, tau, and beta-catenin. This broad activity influences cell cycle progression, apoptosis, DNA damage response, and metabolism. The specific outcomes depend on tissue context and the composition of the regulatory B subunits, which direct substrate recognition and subcellular distribution.

Regulation and disease: PP2A activity is modulated by endogenous inhibitors such as SET and CIP2A, as well as by alterations in subunit expression or mutation. Mutations in PPP2R1A have been reported in several cancers, and reduced PP2A activity is associated with tumor progression and neurodegenerative diseases. In cancer research, strategies to activate PP2A (PP2A-activating drugs) are explored as potential therapeutic approaches.