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Publication : Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities.

First Author  Cho SG Year  2003
Journal  J Cell Biol Volume  163
Issue  1 Pages  71-81
PubMed ID  14557248 Mgi Jnum  J:273504
Mgi Id  MGI:6294156 Doi  10.1083/jcb.200303003
Citation  Cho SG, et al. (2003) Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities. J Cell Biol 163(1):71-81
abstractText  Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3-mediated ICAD cleavage. Overexpressed CIIA reduces H2O2- and tumor necrosis factor-alpha-induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1- and CAD-mediated signaling.
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