Ecdysone receptor directly binds the promoter of the <i>Drosophila</i> caspase <i>dronc</i>, regulating its expression in specific tissues

Cakouros, Dimitrios; Daish, Tasman; Kumar, Sharad

doi:10.1083/jcb.200311057

Cited by 90 publications

(82 citation statements)

References 29 publications

(63 reference statements)

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“…17,26,29 Furthermore, in cultured cells, dronc ablation by RNA interference (RNAi) inhibits cell death induced by ecdysone. 37,38 However, surprisingly, midgut removal and downstream caspase activation in larval midguts occur normally in dronc mutant animals, 26 suggesting that alternative ways of activating effector caspases exists in some cases ( Figure 3). Gene expression and promoter analysis indicate that the dronc gene is regulated by the heterodimeric nuclear receptor EcR/Usp (ecdysone receptor/ultraspiracle) directly in response to ecdysone and also via the ecdysoneinduced transcription factor BR-C. 37,38 CARMER, the fly homologue of the mammalian CARM1 histone methyl transferase, is also recruited to the dronc promoter via the EcR/Usp complex and positively regulates ecdysone-induced dronc expression.…”

Section: Caspasesmentioning

confidence: 99%

Caspase function in programmed cell death

2006

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The first proapoptotic caspase, CED-3, was cloned from Caenorhabditis elegans in 1993 and shown to be essential for the developmental death of all somatic cells. Following the discovery of CED-3, caspases have been cloned from several vertebrate and invertebrate species. As reviewed in other articles in this issue of Cell Death and Differentiation, many caspases function in nonapoptotic pathways. However, as is clear from the worm studies, the evolutionarily conserved role of caspases is to execute programmed cell death. In this article, I will specifically focus on caspases that function primarily in cell death execution. In particular, the physiological function of caspases in apoptosis is discussed using examples from the worm, fly and mammals.

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Section: Caspasesmentioning

confidence: 99%

Caspase function in programmed cell death

2006

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“…EcR/ USP also regulates the transcription of rpr and dronc by directly binding to regions in their promoters (Fig. 2) (Cakouros et al, 2004a, Jiang et al, 2000. Although autophagy is also required for larval salivary gland PCD, of the autophagy genes transcriptionally upregulated during this process, Atg1 is the only identified Atg gene to be directly regulated by EcR/USP (Fig.…”

Section: Salivary Glandsmentioning

confidence: 99%

“…For example, BR-C and E93 appear to regulate the temporal expression of dronc whereas direct binding of the dronc promoter by EcR/USP is important for the spatial expression of this caspase (Cakouros et al, 2004a. Animals which lack the EcR/USP binding element in the dronc promoter do not express dronc in the salivary gland.…”

Section: Salivary Glandsmentioning

confidence: 99%

Ecdysone-mediated programmed cell death in Drosophila

Nicolson

Denton²,

Kumar³

2015

Int. J. Dev. Biol.

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During Drosophila development, the steroid hormone ecdysone plays a key role in the transition from embryo into larva and then into pupa. It is during larval-pupal metamorphosis that extensive programmed cell death occurs to remove large obsolete larval tissues. During this transition, ecdysone pulses control the expression of specific transcription factors which drive the expression of key genes involved in cell death, thus spatially and temporally controlling programmed cell death. Ecdysone also controls cell death in specific larval and adult tissues. This review focuses on the current knowledge of ecdysone-mediated cell death in Drosophila.

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“…Sense and antisense strands were annealed to generate dsRNA, and the quality of RNA was analyzed on a 2.2 M formaldehyde gel. dsRNA (ϳ40 nM) was added to cells in 1 ml of serum-free medium and mixed vigorously as described previously (23)(24)(25). Cells were incubated for 1 h followed by the addition of 2 ml of medium supplemented with 15% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

Ecdysone-mediated Up-regulation of the Effector Caspase DRICE Is Required for Hormone-dependent Apoptosis in Drosophila Cells

Kilpatrick¹,

Cakouros

Kumar

2005

Journal of Biological Chemistry

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The Drosophila steroid hormone ecdysone mediates cell death during metamorphosis by regulating the transcription of a number of cell death genes. The apical caspase DRONC is known to be transcriptionally regulated by ecdysone during development. Here we demonstrate that ecdysone also regulates the transcription of DRICE, a major effector caspase and a downstream target for DRONC in the fly. Using RNA interference in an ecdysone-responsive Drosophila cell line, we show that drice up-regulation is essential for apoptosis induced by ecdysone. We also show that drice expression is specifically controlled by the ecdysone-regulated transcription factor BR-C. Combined with previous observations, our results indicate that transcriptional regulation of the components of the core apoptotic machinery plays a key role in hormone-regulated programmed cell death during Drosophila development.Programmed cell death is necessary to delete superfluous cells in metazoans and to maintain homeostasis (reviewed in Refs. 1 and 2). The core cell death machinery, consisting of the BH3-only proteins, BCL-2 family, caspase adaptors, and caspases, is highly conserved and is present in all metazoan cells (reviewed in Refs. 3-6). As most components of the cell death machinery are present constitutively within a cell, it is widely believed that execution of apoptosis is primarily regulated post-transcriptionally, that is apoptotic signals somehow feed into and activate preexisting caspase machinery. However, recent data suggest that many components of the core apoptosis machinery, including some caspases, are transcriptionally regulated during cell death and that the levels of the prosurvival and proapoptotic factors in the cell may be crucial to activate the apoptotic program (reviewed in Ref. 4). Consistent with this, there is evidence that various signals such as cytotoxic insults, hormones, and growth factors regulate the activation of the death program by controlling the balance between prosurvival and proapoptotic proteins of the core cell death machinery (4). To understand cell death regulation, it is thus essential to understand the transcriptional control of apoptosis execution.Steroid hormones are known to regulate cell survival and cell death in many tissues. Drosophila melanogaster is an ideal model system to study steroid hormone-regulated apoptosis as a single steroid hormone, 20-hydroxyecdysone, regulates cell death during development (reviewed in Refs. 5 and 7-9). Ecdysone binds to its heterodimeric EcR/Usp receptor and transcriptionally regulates a number of primary response genes. Waves of ecdysone, produced at various times during fly development, regulate molting, cell proliferation, differentiation, and death in a highly controlled manner (5, 7-9). During the transition of larva into pupa, an ecdysone pulse toward the end of the third larval instar stage signals puparium formation, followed by a second pulse ϳ12 h later, which initiates head eversion. During this process obsolete larval tissues, such as salivary glands an...

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Ecdysone receptor directly binds the promoter of the Drosophila caspase dronc, regulating its expression in specific tissues

Cited by 90 publications

References 29 publications

Caspase function in programmed cell death

Caspase function in programmed cell death

Ecdysone-mediated programmed cell death in Drosophila

Ecdysone-mediated Up-regulation of the Effector Caspase DRICE Is Required for Hormone-dependent Apoptosis in Drosophila Cells

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