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An apoptosis-promoting factor leads cells to suicide by making them feel homeless. With their report on page 169, Wang et al. finally explain how a long-known death kinase initiates apoptosis.$ b) z/ w( g$ {
% S- Q% P1 \3 M' KThe kinase in question is death associated protein kinase (DAPK), a positive regulator of apoptosis induced by many stimuli, including c-myc and TGF-?. Although DAPK was cloned several years ago, its function in cell death has remained elusive. The new results reveal that DAPK has the unusual ability to initiate anoikis, a form of apoptosis induced in unattached cells, by interfering with integrin signaling.
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9 P: [0 ?0 b! f( iNot one to dally with downstream signals, DAPK starts at the top—by altering integrin structure. Wang et al. found that DAPK locks integrin in an inactive state, thus suppressing epithelial cell adhesion to the extracellular matrix (ECM). As a result, the ECM survival pathway initiated by integrin and mediated by FAK was blocked, resulting in cell death. DAPK effects on adherence and survival were reversed by activating integrin or by expressing active FAK. Carcinoma cells, which are resistant to anoikis, were unaffected by DAPK. Wang et al. do not yet know whether DAPK binds to the cytoplasmic tails of integrin or how it might inactivate the receptor.(Integrin activation (black bars) blocks ) |
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发表于 2009-3-6 00:05
发表于 2015-5-23 12:59
