SET-Protein Phosphatase 2A complex (SET-PP2A)

The SET-PP2A complex is a critical regulatory assembly formed by the interaction between the oncoprotein SET (also known as I2PP2A or SE Translocation) and the tumor suppressor Protein Phosphatase 2A (PP2A) [1, 4]. SET acts as a potent endogenous inhibitor of PP2A, a major serine/threonine phosphatase that maintains cellular homeostasis by dephosphorylating key signaling proteins like Akt, c-Myc, and ERK [3, 7]. In various malignancies, including leukemia and solid tumors, SET is frequently overexpressed, leading to the functional inactivation of PP2A and the subsequent sustained activation of pro-survival and proliferative pathways [1, 13]. Pharmacological strategies aim to disrupt this complex using small molecules or cell-penetrating peptides, such as FTY720 (Fingolimod) or OP449, to reactivate PP2A, thereby inducing apoptosis and inhibiting tumor growth [5, 15, 16]. Beyond oncology, the SET-PP2A complex is implicated in neurodegenerative disorders such as Alzheimer's disease, where SET-mediated inhibition of PP2A contributes to the hyperphosphorylation of tau protein [4, 7, 9].

Other names

SET/I2PP2A-PP2A complexI2PP2A-PP2A complexTAF-Iβ-PP2A complexSE Translocation-Protein Phosphatase 2A complexSET-PP2Ac complex

Disruption of the SET-PP2A interaction to restore the phosphatase activity of Protein Phosphatase 2A (PP2A), thereby promoting the dephosphorylation of oncogenic substrates such as Akt, c-Myc, and ERK [1, 5, 8].