Abstract
Proteasome inhibitors induce cell death and are used in cancer therapy, but little is known about the relationship between proteasome impairment and cell death under normal physiological conditions. Here, we investigate the relationship between proteasome function and larval salivary gland cell death during development in Drosophila. Drosophila larval salivary gland cells undergo synchronized programmed cell death requiring both caspases and autophagy (Atg) genes during development. Here, we show that ubiquitin proteasome system (UPS) function is reduced during normal salivary gland cell death, and that ectopic proteasome impairment in salivary gland cells leads to early DNA fragmentation and salivary gland condensation in vivo. Shotgun proteomic analyses of purified dying salivary glands identified the UPS as the top category of proteins enriched, suggesting a possible compensatory induction of these factors to maintain proteolysis during cell death. We compared the proteome following ectopic proteasome impairment to the proteome during developmental cell death in salivary gland cells. Proteins that were enriched in both populations of cells were screened for their function in salivary gland degradation using RNAi knockdown. We identified several factors, including trol, a novel gene CG11880, and the cop9 signalsome component cop9 signalsome 6, as required for Drosophila larval salivary gland degradation.
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Abbreviations
- UPS:
-
ubiquitin proteasome system
- MS:
-
mass spectrometry
- CSN6:
-
cop9 signalsome 6
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Acknowledgements
We thank P Meier, the Bloomington Stock Center, and the VDRC for Drosophila strains. We thank K Simin for assistance with proteomics data analysis. This work was supported by the NIH grant GM079431 to EHB. EHB is an Ellison Medical Foundation Scholar and a member of the UMass DERC (DK32520).
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McPhee, C., Balgley, B., Nelson, C. et al. Identification of factors that function in Drosophila salivary gland cell death during development using proteomics. Cell Death Differ 20, 218–225 (2013). https://doi.org/10.1038/cdd.2012.110
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DOI: https://doi.org/10.1038/cdd.2012.110
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