Phosphoprotein enriched in astrocytes 15 (PEA-15) (PEA-15)

Phosphoprotein enriched in astrocytes 15 (PEA-15), also known as phosphoprotein enriched in diabetes (PED), is a 15 kDa scaffold protein that is ubiquitously expressed and highly conserved across species [1, 2]. It contains an N-terminal death effector domain (DED) and a C-terminal tail, allowing it to act as a molecular adaptor that integrates signals from various pathways, including those for apoptosis, glucose metabolism, and cell proliferation [2, 5]. PEA-15 is a substrate for multiple kinases, including protein kinase C (PKC) and Akt, which regulate its stability and function through phosphorylation at Ser104 and Ser116 [2, 9]. In type 2 diabetes, PEA-15 is frequently overexpressed, leading to insulin resistance by binding to phospholipase D1 (PLD1) and inhibiting the translocation of the GLUT4 glucose transporter [4, 10]. In cancer, its role is multifaceted; it can function as a tumor suppressor by sequestering ERK1/2 in the cytoplasm to prevent nuclear signaling, or as an anti-apoptotic factor by interfering with the formation of the death-inducing signaling complex (DISC) [1, 11]. Due to its involvement in these critical pathological processes, PEA-15 is considered a promising therapeutic target, with research focusing on small molecules and peptides designed to disrupt its specific protein-protein interactions [10, 13].

Other names

PEDPhosphoprotein enriched in diabetesHMAT1HUMMAT1AMAT1MAT1A

Inhibition of protein-protein interactions (PPI) between PED/PEA-15 and its binding partners, such as Phospholipase D1 (PLD1) to restore insulin sensitivity or Extracellular Signal-Regulated Kinase (ERK1/2) to modulate cell proliferation and apoptosis [4, 10, 11].