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Issue 1010 coverApoptosis from Signaling Pathways to Therapeutic Tools Volume 1010 published December 2003
Ann. N.Y. Acad. Sci. 1010: 43–50 (2003). doi: 10.1196/annals.1299.006
Copyright © 2003 by the New York Academy of Sciences
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Articles by SHARIF, A.
Articles by CHNEIWEISS, H.
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Articles by SHARIF, A.
Articles by CHNEIWEISS, H.
PEA-15 Modulates TNF{alpha} Intracellular Signaling in Astrocytes

ARIANE SHARIF, BRIGITTE CANTON, MARIE-PIERRE JUNIER AND HERVÉ CHNEIWEISS

INSERM U114, Department de Neuropharmacologie, Collège de France, 75231 Paris Cedex 05, France

Address for correspondence: Hervé Chneiweiss, INSERM U114, Chair de Neuropharmacologie, Collège de France, 11 Place M. Berthelot, 75231 Paris Cedex 05, France. Voice: 33-1 44 27 12 19; fax: 33-1 44 27 12 60. herve.chneiweiss{at}college-de-france.fr
Ann. N.Y. Acad. Sci. 1010: 43-50 (2003).

PEA-15 is a small protein (15 kDa) that was first identified as an abundant phosphoprotein in brain astrocytes and subsequently shown to be widely expressed in different tissues and highly conserved among mammals. It is composed of an N-terminal death effector domain (DED) and a C-terminal tail of irregular structure. PEA-15 is regulated by multiple calcium-dependent phosphorylation pathways. PEA-15 is ideally positioned to play a major role in signal integration. Accordingly, it has been demonstrated that PEA-15 diverts astrocytes from TNF{alpha}-triggered apoptosis and regulates the actions of the ERK MAP kinase cascade by binding to ERK and altering its subcellular localization. Expression of PEA-15 directs TNF{alpha} outcomes toward survival, whereas its absence allows the development of the cytokine-induced cell death.

Key Words: PEA-15 • TNFalpha • death effector domain • NF-{kappa}B • ERK MAP kinase




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