驱动细胞死亡和增殖的反馈回路及其在肠干细胞中的缺陷。

IF 3.3 2区 生物学 Q1 BIOLOGY
Shivakshi Sulekh, Yuko Ikegawa, Saki Naito, Asami Oji, Ichiro Hiratani, Sa Kan Yoo
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引用次数: 0

摘要

细胞的死亡和增殖是对立的,但有时也会相互关联。Caspases 传统上被认为执行细胞凋亡,但它也发挥非凋亡作用,但其确切的机制仍然难以捉摸。在这里,我们利用果蝇肠干细胞(ISCs)发现,激活 Caspases 会诱导大量细胞增殖,而不是细胞死亡。我们阐明了在caspases和JNK之间存在一个正反馈回路,可以同时驱动细胞增殖和细胞死亡。在ISCs中,JNK向caspases发出的信号是有缺陷的,这使得平衡向增殖倾斜。从机制上讲,DIAP1抑制剂rpr通过转录和蛋白定位存在两级调控。这项工作提供了一个概念框架,解释了caspases如何在体内发挥凋亡和非凋亡功能,以及ISCs如何实现对细胞死亡的抵抗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A feedback loop that drives cell death and proliferation and its defect in intestinal stem cells.
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.
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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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