Cell death and proliferation are at a glance dichotomic events, but occasionally coupled. Caspases, traditionally known to execute apoptosis, play non-apoptotic roles, but their exact mechanism remains elusive. Here, using Drosophila intestinal stem cells (ISCs), we discovered that activation of caspases induces massive cell proliferation rather than cell death. We elucidate that a positive feedback circuit exists between caspases and JNK, which can simultaneously drive cell proliferation and cell death. In ISCs, signalling from JNK to caspases is defective, which skews the balance towards proliferation. Mechanistically, two-tiered regulation of the DIAP1 inhibitor rpr, through its transcription and its protein localization, exists. This work provides a conceptual framework that explains how caspases perform apoptotic and non-apoptotic functions in vivo and how ISCs accomplish their resistance to cell death.

中文翻译：

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驱动细胞死亡和增殖的反馈回路及其在肠道干细胞中的缺陷。

细胞死亡和增殖乍一看是二分事件，但有时是耦合的。Caspases 传统上已知执行细胞凋亡，但也发挥非细胞凋亡作用，但其确切机制仍然难以捉摸。在这里，我们使用果蝇肠干细胞 (ISC) 发现半胱天冬酶的激活会诱导大量细胞增殖而不是细胞死亡。我们阐明了 caspase 和 JNK 之间存在正反馈回路，可以同时驱动细胞增殖和细胞死亡。在 ISC 中，从 JNK 到半胱天冬酶的信号传导存在缺陷，这会扭曲增殖的平衡。从机制上讲，DIAP1 抑制剂rpr通过其转录和蛋白质定位存在两层调节。这项工作提供了一个概念框架，解释半胱天冬酶如何在体内发挥凋亡和非凋亡功能，以及 ISC 如何实现对细胞死亡的抵抗。