Proliferation and apoptosis adaptor protein 15 (PEA-15)

Proliferation and apoptosis adaptor protein 15 (PEA-15) is a multifunctional, cytoplasmic adapter protein of 15 kDa predominantly identified in astrocytes but expressed ubiquitously in mammalian tissues[6][5]. It contains an N-terminal death effector domain (DED) and a C-terminal region and lacks catalytic activity[5][2]. PEA-15 regulates cell fate by modulating pivotal intracellular signaling pathways: it binds extracellular signal-regulated kinases 1/2 (ERK1/2), thereby sequestering ERK1/2 in the cytoplasm and controlling their access to the nucleus, which impacts cell proliferation and survival[5][6][2][3][4]. The interaction of PEA-15 with ERK1/2 is regulated by phosphorylation of PEA-15; unphosphorylated PEA-15 blocks ERK1/2 nuclear translocation and cell proliferation, while phosphorylated PEA-15 promotes anti-apoptotic functions by interacting with Fas-associated death domain (FADD) protein[3][5][6]. PEA-15 also acts as an endosomal adapter for integrins, regulating integrin endocytosis and subcellular trafficking to Rab5+ endosomes, with implications for cell adhesion and migration, especially in cancer cells[1]. Altered expression or function of PEA-15 has been associated with multiple diseases, notably cancer, diabetes, and neurological and cardiovascular diseases, marking it as a potential therapeutic and diagnostic target in these contexts[6]. No specific drugs directly target PEA-15 at this time.

Other names

Astrocytic phosphoprotein PEA-15Phosphoprotein enriched in astrocytes 15 kDaPEDHMAT1MAT1MAT1HPED-PEA15PED/PEA15Phosphoprotein enriched in diabeteshomolog of mouse MAT-1 oncogenemammary transforming gene 1phosphoprotein enriched in diabetesHUMMAT1H