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We explore the role of apoptosis signal-regulating kinase 1 (ASK1) in A\u03b2-induced death in primary cultures of murine CECs. A\u03b2 induced ASK1 dephosphorylation, which could be prevented by selective inhibition of protein phosphatase 2A (PP2A) but not PP2B. ASK1 dephosphorylation resulted in its dissociation from 14-3-3. ASK1, released from 14-3-3 inhibition, activated p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. p53, a proapoptotic transcription factor, in turn transactivated the expression of Bax, a proapoptotic protein. Transfection with various dominant-negative mutants (DNs), including ASK1 DN and p38MAPK DN, suppressed A\u03b2-induced p38MAPK activation, p53 phosphorylation, and Bax upregulation and partially prevented CEC death. Bax knockdown using a<jats:italic>bax<\/jats:italic>small interfering RNA strategy also reduced Bax expression and subsequent CEC death. These results suggest that A\u03b2 activates the ASK1\u2013p38MAPK\u2013p53\u2013Bax cascade to cause CEC death in a PP2A-dependent manner.<\/jats:p>","DOI":"10.1523\/jneurosci.1874-06.2007","type":"journal-article","created":{"date-parts":[[2007,5,23]],"date-time":"2007-05-23T23:18:51Z","timestamp":1179962331000},"page":"5719-5729","source":"Crossref","is-referenced-by-count":76,"title":["Apoptosis Signal-Regulating Kinase 1 in Amyloid \u03b2 Peptide-Induced Cerebral Endothelial Cell Apoptosis"],"prefix":"10.1523","volume":"27","author":[{"given":"Ming-Jen","family":"Hsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung 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