Abstract
The Drosophila gene putzig (pzg) encodes a nuclear protein that is an integral component of the Trf2/Dref complex involved in the transcription of proliferation-related genes. Moreover, Pzg is found in a complex together with the nucleosome remodeling factor NURF, where it promotes Notch target gene activation. Here we show that downregulation of pzg activity in the developing wing imaginal discs induces an apoptotic response, accompanied by the induction of the pro-apoptotic gene reaper, repression of Drosophila inhibitor of apoptosis protein accumulation and the activation of the caspases Drice, Caspase3 and Dcp1. As a further consequence ‘Apoptosis induced Proliferation’ (AiP) and ‘Apoptosis induced Apoptosis’ (AiA) are triggered. As expected, the activity of the stress kinase Jun N-terminal kinase (JNK), proposed to mediate both processes, is ectopically induced in response to pzg loss. In addition, the expression of the mitogen wingless (wg) but not of decapentaplegic (dpp) is observed. We present evidence that downregulation of Notch activates Dcp1 caspase and JNK signaling, however, neither induces ectopic wg nor dpp expression. In contrast, the consequences of Dref-RNAi were largely indistinguishable from pzg-RNAi with regard to apoptosis induction. Moreover, overexpression of Dref ameliorated the downregulation of pzg compatible with the notion that the two are required together to maintain cell and tissue homeostasis in Drosophila.
Highlights
Cellular and tissue homeostasis describes a complex process ensuring the survival and correct development of an organism
Pzg is a nuclear protein found in different multimeric complexes including the Trf2/DNA replication-related element-binding factor (Dref) complex and the NURF complex
The Pzg/NURF complex has been implied in the epigenetic regulation of N and EcR target genes [41,76], whereas Dref is involved in the regulation of replication and proliferation related genes
Summary
Cellular and tissue homeostasis describes a complex process ensuring the survival and correct development of an organism. The major form of programmed cell death, contributes to tissue homeostasis by eliminating aberrant, surplus or malignant cells during 'normal' development and in response to stress induced conditions. This safeguarding system demands a fine-tuned control as an unregulated apoptosis has been connected to various human diseases including cancer (reviewed in [1,2,3,4]). Research in several model organisms including Drosophila has expanded our knowledge on the molecular mechanisms underlying the well conserved apoptotic execution program in metazoans: Under normal conditions, cell survival is PLOS ONE | DOI:10.1371/journal.pone.0124652. If cell death is triggered, e.g. under cellular stress conditions, pro-apoptotic gene activity is induced in Drosophila: Pro-apoptotic gene products include the DIAP1-antagonists Hid, Rpr and Grim, which themselves mediate the ubiquitin dependent degradation of DIAP1 thereby enabling caspases to provoke the death of the cell [7,8,9,10,11,12,13]
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