ArticlePLoS genetics2017
An inhibitory mono-ubiquitylation of the Drosophila initiator caspase Dronc functions in both apoptotic and non-apoptotic pathways.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- AlphaFold3-based modeling uncovers the dynamic structural interface between full-length IAP antagonists and DIAP1 for apoptosis regulation in Drosophila.Cell communication and signaling : CCS · 2026Article
- Apoptosis-resistant cells drive compensatory proliferation via cell-autonomous and non-autonomous functions of the initiator caspase Dronc.Nature communications · 2025Article
- Article
- Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity.bioRxiv : the preprint server for biology · 2024Article
- Wg/Wnt1 and Erasp link ER stress to proapoptotic signaling in an autosomal dominant retinitis pigmentosa model.Experimental & molecular medicine · 2023Article
- Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues.International journal of molecular sciences · 2023Article
- Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation.PLoS genetics · 2022Article
- In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening.Journal of visualized experiments : JoVE · 2022Article
- A Mini Review on Molecules Inducing Caspase-Independent Cell Death: A New Route to Cancer Therapy.Molecules (Basel, Switzerland) · 2022Review
- Non-Apoptotic Role of Apoptotic Caspases in theFrontiers in cell and developmental biology · 2022Review
- Non-apoptotic enteroblast-specific role of the initiator caspase Dronc for development and homeostasis of the Drosophila intestine.Scientific reports · 2021Article
- Review
- Transiently "Undead" Enterocytes Mediate Homeostatic Tissue Turnover in the Adult Drosophila Midgut.Cell reports · 2020Article
- Two Sides of the Same Coin - Compensatory Proliferation in Regeneration and Cancer.Advances in experimental medicine and biology · 2019Review
- Ionizing radiation induces stem cell-like properties in a caspase-dependent manner in Drosophila.PLoS genetics · 2018Article
- The many fates of tissue regeneration.PLoS genetics · 2018Article
- Non-apoptotic Caspase regulation of stem cell properties.Seminars in cell & developmental biology · 2018Review
- Caspases maintain tissue integrity by an apoptosis-independent inhibition of cell migration and invasion.Nature communications · 2018Article
- Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions.Developmental cell · 2018Article
- Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.Cell death and differentiation · 2018Review
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4 authors at 3 institutions in 2 countries.
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Abstract
Apoptosis is an evolutionary conserved cell death mechanism, which requires activation of initiator and effector caspases. The Drosophila initiator caspase Dronc, the ortholog of mammalian Caspase-2 and Caspase-9, has an N-terminal CARD domain that recruits Dronc into the apoptosome for activation. In addition to its role in apoptosis, Dronc also has non-apoptotic functions such as compensatory proliferation. One mechanism to control the activation of Dronc is ubiquitylation. However, the mechanistic details of ubiquitylation of Dronc are less clear. For example, monomeric inactive Dronc is subject to non-degradative ubiquitylation in living cells, while ubiquitylation of active apoptosome-bound Dronc triggers its proteolytic degradation in apoptotic cells. Here, we examined the role of non-degradative ubiquitylation of Dronc in living cells in vivo, i.e. in the context of a multi-cellular organism. Our in vivo data suggest that in living cells Dronc is mono-ubiquitylated on Lys78 (K78) in its CARD domain. This ubiquitylation prevents activation of Dronc in the apoptosome and protects cells from apoptosis. Furthermore, K78 ubiquitylation plays an inhibitory role for non-apoptotic functions of Dronc. We provide evidence that not all of the non-apoptotic functions of Dronc require its catalytic activity. In conclusion, we demonstrate a mechanism whereby Dronc's apoptotic and non-apoptotic activities can be kept silenced in a non-degradative manner through a single ubiquitylation event in living cells.
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