Protein phosphatase methylesterase 1 (PME-1) (PME-1)

Protein phosphatase methylesterase 1 (PME-1) is a specialized enzyme that regulates the activity and assembly of Protein phosphatase 2A (PP2A), one of the most abundant serine/threonine phosphatases in the cell [UniProt: Q9Y570]. PME-1 functions by demethylating the C-terminal leucine 309 residue of the PP2A catalytic subunit (PP2Ac), a modification that leads to the dissociation of specific regulatory subunits and the inactivation of the phosphatase complex [PubMed: 11313946]. This regulatory mechanism is crucial for maintaining cellular homeostasis, as PP2A acts as a major tumor suppressor by dephosphorylating key signaling proteins in the Akt, MAPK, and MYC pathways [PubMed: 23541335]. In various malignancies, such as glioblastoma and lung cancer, PME-1 is frequently overexpressed, resulting in the functional inactivation of PP2A and the promotion of uncontrolled cell proliferation and survival [PubMed: 21454756]. Therapeutic strategies targeting the PME-1/PP2A complex focus on small-molecule inhibitors of PME-1, such as ABL-127, which aim to restore PP2A's tumor-suppressive function by increasing its methylation and promoting the formation of active heterotrimeric complexes [PubMed: 24631444]. Beyond oncology, PME-1-mediated regulation of PP2A is also implicated in neurodegenerative conditions like Alzheimer's disease, where PP2A dysfunction contributes to the hyperphosphorylation of Tau protein [PubMed: 12551918].

Other names

PPME1Protein phosphatase 2A methyl esterasePME1Protein phosphatase methylesterase 1PP2A methylesterase / PP2A complex

Inhibition of PME-1 prevents the demethylation of the Protein phosphatase 2A (PP2A) catalytic subunit, thereby stabilizing the active PP2A holoenzyme and enhancing its phosphatase activity against oncogenic substrates [PubMed: 21454756, 24631444].