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;27...

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Bibliographic Details
Published in:Biochemical pharmacology 2003-10, Vol.66 (8), p.1581-1588
Main Authors: Renault, François, Formstecher, Etienne, Callebaut, Isabelle, Junier, Marie-Pierre, Chneiweiss, Hervé
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Astrocytes - cytology
Astrocytes - metabolism
Biological and medical sciences
Calcium-dependent kinases
Cell Cycle - physiology
Death effector domain
Humans
Intracellular Signaling Peptides and Proteins
MAP kinases
Medical sciences
PEA-15
Pharmacology. Drug treatments
Phosphoproteins - genetics
Phosphoproteins - physiology
TNFalpha
Transcription, Genetic
Tumor Necrosis Factor-alpha - physiology
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Summary: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.
ISSN:0006-2952
1873-2968
DOI:10.1016/S0006-2952(03)00514-8