Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms

Yoo, Soon Ji; Huh, Jun R.; Muro, Israel; Hong, Yuling; Wang, Limin; Wang, Susan L.; Feldman, R. M. Renny; Clem, Rollie J.; Müller, H.‐Arno J.; Hay, Bruce A.

doi:10.1038/ncb793

Cited by 351 publications

(342 citation statements)

References 43 publications

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“…14,15 Our collective data argued that the alternative mechanism of action of Reaper in human cells likewise involved inhibition of protein translation. Metabolic labelling experiments indicated that in the presence of DIBM Reaper, new synthesis of XIAP was impeded (results not shown).…”

Section: Reaper and Dibm Reaper Globally Suppress Protein Synthesismentioning

confidence: 93%

“…Binding of Reaper to DIAP1 leads to auto-ubiquitination and proteasomal degradation of DIAP1 instead, thus facilitating Dronc stabilisation and activation. [10][11][12][13][14][15] Other Drosophila proteins share the ability to neutralise DIAP function. These include Grim and Hid as well as the recently identified DNA damage response protein Sickle, whose gene maps adjacent to the H99 region.…”

Section: Introductionmentioning

confidence: 99%

“…17 This so-called IAP-binding motif (IBM) is also present in the mature form of Jafrac2. 19 Loss of DIAP1 results in early embryonic death, also in the absence of the H99 region encoding Reaper, Grim and Hid, 14 indicating that removal of caspase inhibition is sufficient to trigger apoptosis in Drosophila.…”

Section: Introductionmentioning

confidence: 99%

“…In Drosophila, removal of IAP-mediated caspase inhibition is sufficient to cause apoptosis. 14,25 In mammalian cells, however, removal of IAP-mediated inhibition sensitises cells to apoptosis but does not trigger caspase activation and apoptosis. 21,22 An additional signal is required for caspase activation.…”

Section: Introductionmentioning

confidence: 99%

“…14,15 It is presently unknown which structural motifs in Reaper and Grim are responsible for this activity and how it relates to their capacity to induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of action of Drosophila Reaper in mammalian cells: Reaper globally inhibits protein synthesis and induces apoptosis independent of mitochondrial permeability

et al. 2004

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Drosophila Reaper can bind inhibitor of apoptosis proteins (IAP) and thereby rescue caspases from proteasomal degradation. In insect cells, this is sufficient to induce apoptosis. Reaper can also induce apoptosis in mammalian cells, in which caspases need to be activated, usually via the mitochondrial pathway. Nevertheless, we find that Reaper efficiently induces apoptosis in mammalian cells in the absence of mitochondrial permeabilisation and cytochrome c release. Moreover, this capacity was only marginally affected by deletion of Reaper's amino-terminal IAP-binding motif. Independent of this motif, Reaper could globally suppress protein synthesis. Deletion of 20 amino acids from the carboxy-terminus of Reaper fully abrogated its potential to inhibit protein synthesis and to induce apoptosis in the absence of IAP-binding. Our findings indicate that the newly identified capacity of Reaper to suppress protein translation can operate in mammalian cells and may be key to its proapoptotic activity.

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Section: Reaper and Dibm Reaper Globally Suppress Protein Synthesismentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…14,15 It is presently unknown which structural motifs in Reaper and Grim are responsible for this activity and how it relates to their capacity to induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of action of Drosophila Reaper in mammalian cells: Reaper globally inhibits protein synthesis and induces apoptosis independent of mitochondrial permeability

et al. 2004

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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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Targeting the Survivin Pathway for Rational Cancer Therapy

Altieri¹

2006

Apoptosis and Cancer Therapy

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Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms

Cited by 351 publications

References 43 publications

Mechanism of action of Drosophila Reaper in mammalian cells: Reaper globally inhibits protein synthesis and induces apoptosis independent of mitochondrial permeability

Mechanism of action of Drosophila Reaper in mammalian cells: Reaper globally inhibits protein synthesis and induces apoptosis independent of mitochondrial permeability

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

Targeting the Survivin Pathway for Rational Cancer Therapy

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