DRONC coordinates cell death and compensatory proliferation
DRONC coordinates cell death and compensatory proliferation
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DOI：
10.1128/mcb.00183-06
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发表时间：
2006-10-01
影响因子：
5.3
通讯作者：
Miura, Masayuki
中科院分区：
文献类型：
--
作者：
Kondo, Shu;Senoo-Matsuda, Nanami;Miura, Masayuki
意外的细胞死亡往往导致代偿性增殖。例如，在果蝇的成虫盘中，γ射线照射诱导广泛的细胞死亡，这很快被增殖的增加所补偿。过度的代偿性增殖可以由"不死细胞"人工诱导，所述"不死细胞"通过在凋亡刺激物存在下抑制效应物半胱天冬酶而保持存活。这表明，作为凋亡程序的一部分，死亡细胞诱导了代偿性增殖。在这里，我们提供了遗传学证据表明，果蝇启动caspase DRONC管细胞凋亡的执行和随后的补偿性增殖。我们研究了五种果蝇caspase的突变体，并确定了启动caspase DRONC和效应caspase DRICE作为细胞凋亡的关键执行者。Reaper和p35共表达诱导的人工补偿性增殖在雄蜂突变体中被完全抑制。此外，γ射线照射后的补偿性增殖在DRONC被激活但细胞仍然存活的突变体中得到增强。这些结果表明，细胞凋亡途径在DRONC处分叉，并且DRONC协调细胞死亡和补偿性增殖的执行。
Accidental cell death often leads to compensatory proliferation. In Drosophila imaginal discs, for example, gamma-irradiation induces extensive cell death, which is rapidly compensated by elevated proliferation. Excessive compensatory proliferation can be artificially induced by "undead cells" that are kept alive by inhibition of effector caspases in the presence of apoptotic stimuli. This suggests that compensatory proliferation is induced by dying cells as part of the apoptosis program. Here, we provide genetic evidence that the Drosophila initiator caspase DRONC governs both apoptosis execution and subsequent compensatory proliferation. We examined mutants of five Drosophila caspases and identified the initiator caspase DRONC and the effector caspase DRICE as crucial executioners of apoptosis. Artificial compensatory proliferation induced by coexpression of Reaper and p35 was completely suppressed in drone mutants. Moreover, compensatory proliferation after gamma-irradiation was enhanced in drice mutants, in which DRONC is activated but the cells remain alive. These results show that the apoptotic pathway bifurcates at DRONC and that DRONC coordinates the execution of cell death and compensatory proliferation.