Protein phosphatase 2A holoenzyme containing B56 delta regulatory subunit (PP2A-B56δ)

The Protein Phosphatase 2A (PP2A) holoenzyme containing the B56 delta (Bδ) regulatory subunit is a major serine/threonine phosphatase complex essential for maintaining cellular homeostasis. It is a heterotrimer composed of a catalytic C subunit, a structural A subunit, and the B56δ regulatory subunit (encoded by the PPP2R5D gene), which dictates substrate specificity and subcellular localization. This specific holoenzyme plays a critical role in regulating key signaling pathways, including the PI3K/AKT and MAPK pathways, and is vital for proper brain development and cell cycle progression. Mutations in the PPP2R5D subunit are primary drivers of Jordan's Syndrome, a neurodevelopmental disorder characterized by intellectual disability and macrocephaly. In oncology, PP2A-B56δ often functions as a tumor suppressor; its inactivation or downregulation is associated with various cancers, making the restoration of its activity via Small Molecule Activators of PP2A (SMAPs) a promising therapeutic strategy. Conversely, PP2A inhibitors like LB-100 are being explored to enhance the efficacy of DNA-damaging agents in cancer treatment.

Other names

PP2A-B56-deltaPPP2R5D-containing PP2A complexProtein phosphatase 2 regulatory subunit B' deltaB56DPP2A-B'delta

PP2A-B56δ acts as a heterotrimeric phosphatase that dephosphorylates specific serine/threonine residues on target proteins such as AKT, MYC, and Tau. Therapeutic strategies involve either inhibiting the enzyme to sensitize cancer cells to chemotherapy (e.g., LB-100) or using Small Molecule Activators of PP2A (SMAPs) to restore its tumor-suppressive function by stabilizing the holoenzyme assembly.