The multifunctional protein PEA-15 is involved in the control of apoptosis and cell cycle in astrocytes.
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.
Renault
François
F
INSERM U114, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France.
Formstecher
Etienne
E
Callebaut
Isabelle
I
Junier
Marie-Pierre
MP
Chneiweiss
Hervé
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha