Global ETD Search

1	Interaction of Hippo Pathway and Dronc to Regulate Organ Size in Drosophila melanogaster Verghese, Shilpi January 2014 (has links) No description available. Biology
2	Regulation of the Drosophila Initiator Caspase Dronc through Ubiquitylation Kamber Kaya, Hatem E. 17 January 2017 (has links) Apoptosis is a programmed cell death mechanism that is evolutionary conserved from worms to humans. Apoptosis is mediated by initiator and effector caspases. The initiator caspases carry long pro-domains for their interaction with scaffolding proteins to form a cell-death platform, which is essential for their activation. Activated initiator caspases then cleave effector caspases that execute cell death through cleaving downstream targets. In addition to their apoptotic function, caspases also participate in events where caspase activity is not required for cell killing, but for regulating other functions, so-called non-apoptotic functions of caspases. The Drosophila initiator caspase Dronc, the ortholog of mammalian caspase-2 and caspase-9 has a CARD domain that is essential for its interaction with the scaffolding protein Dark to form the apoptosome. Apoptosome formation is crucial for activation of Dronc. Activity of both initiator and effector caspases are further kept in control by the ubiquitin system to avoid inappropriate caspase activity. However, mechanistic details of how the ubiquitin system regulates activation of Dronc are not clear. Therefore, I investigated the ubiquitylation status of Dronc and its function in Drosophila. I found that Dronc is mono-ubiquitylated at Lys78 (K78) in its CARD domain, which blocks its interaction with Dark and formation of the apoptosome. Furthermore, I demonstrated that K78 mono-ubiquitylation plays an inhibitory role in Dronc’s non-apoptotic functions, which may not require its catalytic activity but may be important for the survival of the fly. This thesis study unveils the link between the ubiquitin system and caspases through a regulatory mechanism where a single mono-ubiquitylation event could inhibit both apoptotic and non-apoptotic functions of a caspase. Apoptosis Ubiquitin Drosophila Dronc Caspases Cell Death Post-Translational Modifications (PTMs) Apoptosome Biochemistry Cell and Developmental Biology Molecular Biology Molecular Genetics
3	Regulation of Dronc Transcription by the Hippo and Ecdysone Pathways in Drosophila Melanogaster Gangwani, Karishma 11 August 2022 (has links) No description available. Biology Dronc Hippo Pathway Ecdysone Signaling Neuroblast Stem Cells Glioblaatoma Tep1 Yorkie Scalloped Cell death Cell proliferation
4	Death is Not the End: The Role of Reactive Oxygen Species in Driving Apoptosis-induced Proliferation Fogarty, Caitlin E. 02 June 2015 (has links) Apoptosis-induced proliferation (AiP) is a compensatory mechanism to maintain tissue size and morphology following unexpected cell loss during normal development, and may also be a contributing factor to cancer growth and drug resistance. In apoptotic cells, caspase-initiated signaling cascades lead to the downstream production of mitogenic factors and the proliferation of neighboring surviving cells. In epithelial Drosophila tissues, the Caspase-9 homolog Dronc drives AiP via activation of Jun N-terminal kinase (JNK); however, the specific mechanisms of JNK activation remain unknown. Using a model of sustained AiP that produces a hyperplastic phenotype in Drosophila eye and head tissue, I have found that caspase-induced activation of JNK during AiP depends on extracellular reactive oxygen species (ROS) generated by the NADPH oxidase Duox. I found these ROS are produced early in the death-regeneration process by undifferentiated epithelial cells that have initiated the apoptotic cascade. I also found that reduction of these ROS by mis-expression of extracellular catalases was sufficient to reduce the frequency of overgrowth associated with our model of AiP. I further observed that extracellular ROS attract and activate Drosophila macrophages (hemocytes), which may in turn trigger JNK activity in epithelial cells by signaling through the TNF receptor Grindelwald. We propose that signaling back and forth between epithelial cells and hemocytes by extracellular ROS and Grindelwald drives compensatory proliferation within the epithelium, and that in cases of persistent signaling, such as in our sustained model of AiP, hemocytes play a tumor promoting role, driving overgrowth. Apoptosis Apoptosis-induced Proliferation Cancer Caspase Catalase Cell death Chronic Inflammation c-Jun Kinase (JNK) Signaling Dcp-1 DrICE Drosophila Dronc Duox Hemocytes Imaginal Discs Non-apoptotic functions Phoenix Rising Reactive Oxygen Species Regeneration Regulatory Feedback Loop TNF Signaling Tumor Associated Macrophages Wound Healing Cancer Biology Developmental Biology

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