The multifunctional protein PEA-15 is involved in the control of apoptosis and cell cycle in astrocytes

Biochem Pharmacol. 2003 Oct 15;66(8):1581-8. doi: 10.1016/s0006-2952(03)00514-8.


PEA-15 is a small protein (15 kDa) that was first identified as an abundant phosphoprotein in brain astrocytes [Araujo et al., J Biol Chem 1993;268(8):5911-20], and subsequently shown to be widely expressed in different tissues and highly conserved among mammals [Estelles et al., J Biol Chem 1996;271(25):14800-6; Danziger et al., J Neurochem 1995;64(3):1016-25]. It is composed of a N-terminal death effector domain and a C-terminal tail of irregular structure. PEA-15 is regulated by multiple calcium-dependent phosphorylation pathways that account for its different forms: a non-phosphorylated form in equilibrium with a mono and a biphosphorylated variety. This already suggested that PEA-15 may play a major role in signal integration. Accordingly, it has been demonstrated to modulate signaling pathways that control apoptosis and cell proliferation. In particular, PEA-15 diverts astrocytes from TNFalpha-triggered apoptosis and regulates the actions of the ERK MAP kinase cascade by binding to ERK and altering its subcellular localization. The three-dimensional structure of PEA-15 has been modelized and recently determined using NMR spectroscopy, and may help to understand the various functions played by the protein through its molecular interactions.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Astrocytes / cytology*
  • Astrocytes / metabolism
  • Cell Cycle / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / physiology


  • Apoptosis Regulatory Proteins
  • Intracellular Signaling Peptides and Proteins
  • PEA15 protein, human
  • Phosphoproteins
  • Tumor Necrosis Factor-alpha