DOI: 10.26508/lsa.202302238 ISSN: 2575-1077

A feedback loop that drives cell death and proliferation and its defect in intestinal stem cells

Shivakshi Sulekh, Yuko Ikegawa, Saki Naito, Asami Oji, Ichiro Hiratani, Sa Kan Yoo
  • Health, Toxicology and Mutagenesis
  • Plant Science
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Ecology

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, usingDrosophilaintestinal 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 inhibitorrpr, 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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