Compensatory Proliferation in Drosophila Imaginal Discs Requires Dronc-Dependent p53 Activity

Wells, Brent S.; Yoshida, Eri; Johnston, Laura

doi:10.1016/j.cub.2006.07.046

Cited by 177 publications

(260 citation statements)

References 46 publications

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“…Johnston and colleagues 7 have proposed that Dp53 gene promotes the expression of mitogens, such as Wg, which is required for apoptosisinduced proliferation. However, the specific roles of the Dp53 and DDNp53 isoforms in activating Wg have not been defined.…”

Section: Resultsmentioning

confidence: 99%

“…Drosophila p53 gene is proposed to act in a feedback loop to self-amplify and promote apoptosis-induced proliferation. 7,34 Therefore, we wanted to examine how the endogenous p53 gene contributes to the observed overexpression phenotype. We produced DDNp53 or Dp53 in p53-null flies.…”

Section: Resultsmentioning

confidence: 99%

“…4,36,37 Although more clearly detected in 'undead cells', mitogen gene expression and extra proliferation have also been detected in genuine apoptotic cells. 4,36,38 It was proposed that the initiator caspase Dronc leads to Dp53 expression, which in turn activates mitogen gene expression, 7,34 but the specific roles of Dp53 and DDNp53 remain to be established. Here we showed that DDNp53 is a potent inducer of wg expression both in the 'undead cell' and genuine apoptotic cell models (Figures 3-5).…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Apoptosis-induced proliferation requires Drosophila p53 and the caspase Dronc, and involves the release of mitogens such as Wingless (Wg) and Decapentaplegic (Dpp) that induce the growth of the surrounding tissues. [6][7][8] Apoptosis-induced proliferation has also been observed in hydra, where dying cells express Wnt that is required for cell division. 9 A recent study showed that when injected into mice, irradiated mouse embryonic fibroblasts can induce sustained growth of feeder tumour cells.…”

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confidence: 99%

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Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation

Dichtel-Danjoy

Dourlen

et al. 2012

Cell Death Differ

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Irradiated or injured cells enter apoptosis, and in turn, promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells have an active role in proliferation, where the caspase Dronc and p53 induce mitogen expression and growth in the surrounding tissues. The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-terminally truncated isoform (DΔNp53). Historically, DΔNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that DΔNp53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and DΔNp53 in apoptosis and apoptosis-induced proliferation. We found that both isoforms were capable of activating apoptosis, but that they each induced distinct IAP antagonists. Expression of DΔNp53 induced Wingless (Wg) expression and enhanced proliferation in both 'undead cells' and in 'genuine' apoptotic cells. In contrast to DΔNp53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that DΔNp53 is the main isoform that regulates apoptosis-induced proliferation. Understanding the roles of Drosophila p53 isoforms in apoptosis and in apoptosis-induced proliferation may shed new light on the roles of p53 isoforms in humans, with important implications in cancer biology

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation

Dichtel-Danjoy

Dourlen

et al. 2012

Cell Death Differ

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“…Instead, Dronc activity is required for compensatory proliferation and functions to promote expression of the mitogens Wingless (Wg) and Decapentaplegic (Dpp) to promote proliferation of neighboring cells. [108][109][110] The effector caspases Drice and Dcp-1 can also induce compensatory proliferation in differentiating eye tissue, by activation of the Hedgehog signaling pathway. 106 These studies demonstrated critical roles for caspases in coordinating both cell death and proliferation during development and regeneration, and provided the first in vivo evidence for a nonapoptotic function for an initiator-apoptotic caspase.…”

Section: Caspases In Cell Proliferation and Tissue Regenerationmentioning

confidence: 99%

Old, new and emerging functions of caspases

et al. 2014

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Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.

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Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system

2016

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Edited by Wilhelm JustNervous system development is a process that integrates cell proliferation, differentiation, and programmed cell death (PCD). PCD is an evolutionary conserved mechanism and a fundamental developmental process by which the final cell number in a nervous system is established. In vertebrates and invertebrates, PCD can be determined intrinsically by cell lineage and age, as well as extrinsically by nutritional, metabolic, and hormonal states. Drosophila has been an instrumental model for understanding how this mechanism is regulated. We review the role of PCD in Drosophila central nervous system development from neural progenitors to neurons, its molecular mechanism and function, how it is regulated and implemented, and how it ultimately shapes the fly central nervous system from the embryo to the adult. Finally, we discuss ideas that emerged while integrating this information.Keywords: apoptosis; Drosophila; neurodevelopment Apoptosis shapes Drosophila neural development from the emergence of neuroectoderm in the embryo to the eclosing adult. The earliest indication of programmed cell death (PCD) during neurodevelopment is at embryonic stages 11-12 [1-3], when the first neurons and epidermal cells die [4,5]. Neuronal apoptosis then increases dramatically peaking at embryonic stages 16-17, when the ventral nerve cord (VNC) condenses [3] and the embryo produces its first twitching movements [1]. Although the observed amount of neuronal death differs from embryo to embryo [5], symmetry in neuronal PCD is often observed between the right and left sides of a single embryo [1], indicating that both deterministic and 'random' processes participate in the selection of surviving neurons.Programmed cell death in Drosophila neural development comes in different flavors. It can be triggered by spatial, temporal, nutritional, hormonal, and metabolic signals; it can be regulated by Hox genes, Notch, and other signaling pathways; it can be mediated by one or more proapoptotic genes; and it can act at the stage of neural precursors, of newly born or of mature neurons/glia. What is clear is that dying is not trivial for a cell. Many layers of regulation exist that ensure

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Compensatory Proliferation in Drosophila Imaginal Discs Requires Dronc-Dependent p53 Activity

Cited by 177 publications

References 46 publications

Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation

Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation

Old, new and emerging functions of caspases

Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system

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