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Death-Associated Protein Kinase-Mediated Cell Death Modulated by Interaction with DANGER

2010; Society for Neuroscience; Volume: 30; Issue: 1 Linguagem: Inglês

10.1523/jneurosci.3974-09.2010

1529-2401

Bingnan N. Kang, Abdullah Shafique Ahmad, Sofiyan Saleem, Randen L. Patterson, Lynda D. Hester, Sylvain Doré, Solomon H. Snyder,

Autophagy in Disease and Therapy

Death-associated protein kinase (DAPK) is a key player in multiple cell death signaling pathways. We report that DAPK is regulated by DANGER, a partial MAB-21 domain-containing protein. DANGER binds directly to DAPK and inhibits DAPK catalytic activity. DANGER-deficient mouse embryonic fibroblasts and neurons exhibit greater DAPK activity and increased sensitivity to cell death stimuli than do wild-type control cells. In addition, DANGER-deficient mice manifest more severe brain damage after acute excitotoxicity and transient cerebral ischemia than do control mice. Accordingly, DANGER may physiologically regulate the viability of neurons and represent a potential therapeutic target for stroke and neurodegenerative diseases.