A balance between the diap1 death inhibitor and reaper and hid death inducers controls steroid-triggered cell death in Drosophila
A balance between the diap1 death inhibitor and reaper and hid death inducers controls steroid-triggered cell death in Drosophila
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DOI：
10.1073/pnas.0402647101
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发表时间：
2004-05-25
影响因子：
11.1
通讯作者：
Thummel, CS
中科院分区：
文献类型：
--
作者：
Yin, VP;Thummel, CS
在果蝇蜕变过程中，类固醇激素蜕皮激素对过时幼虫组织的大量破坏起指导作用，为定义类固醇调节的程序性细胞死亡的分子机制提供了一个模型系统。虽然早期的研究已经确定蜕皮激素触发的遗传级联反应立即发生在幼虫组织细胞死亡之前，但没有死亡调节基因在功能上与这种死亡反应相关。我们发现蜕皮激素诱导的死亡激活因子基因死神（reaper, rpr）和头退化缺陷（head involution defective, hid）的表达是幼虫蜕变过程中中肠和唾液腺破坏所必需的，其中hid在唾液腺和rpr中起主要作用，而hid在中肠中起冗余作用。我们还发现果蝇细胞凋亡1抑制剂是幼虫细胞死亡途径中的一个存活因子，延迟死亡，直到其抑制作用被rpr和hid克服。本研究揭示了rpr和hid在果蝇细胞死亡反应中的功能相互作用，并提供证据表明，在果蝇细胞凋亡抑制剂1与rpr和hid死亡激活因子之间的平衡发生类固醇触发的变化，从而实现了蜕变过程中幼虫组织细胞死亡的精确时间。
The steroid hormone ecdysone directs the massive destruction of obsolete larval tissues during Drosophila metamorphosis, providing a model system for defining the molecular mechanisms of steroid-regulated programmed cell death. Although earlier studies have identified an ecdysone triggered genetic cascade that immediately precedes larval tissue cell death, no death regulatory genes have been functionally linked to this death response. We show here that ecdysone-induced expression of the death activator genes reaper (rpr) and head involution defective (hid) is required for destruction of the larval midgut and salivary glands during metamorphosis, with hid playing a primary role in the salivary glands and rpr and hid acting in a redundant manner in the midguts. We also identify the Drosophila inhibitor of apoptosis 1 as a survival factor in the larval cell death pathway, delaying death until its inhibitory effect is overcome by rpr and hid. This study reveals functional interactions between rpr and hid in Drosophila cell death responses and provides evidence that the precise timing of larval tissue cell death during metamorphosis is achieved through a steroid-triggered shift in the balance between the Drosophila inhibitor of apoptosis 1 and the rpr and hid death activators.