Journal article
Systematic In Vivo RNAi Analysis Identifies IAPs as NEDD8-E3 Ligases
M Broemer, T Tenev, KTG Rigbolt, S Hempel, B Blagoev, J Silke, M Ditzel, P Meier
Molecular Cell | CELL PRESS | Published : 2010
Abstract
The intimate relationship between mediators of the ubiquitin (Ub)-signaling system and human diseases has sparked profound interest in how Ub influences cell death and survival. While the consequence of Ub attachment is intensely studied, little is known with regards to the effects of other Ub-like proteins (UBLs), and deconjugating enzymes that remove the Ub or UBL adduct. Systematic in vivo RNAi analysis identified three NEDD8-specific isopeptidases that, when knocked down, suppress apoptosis. Consistent with the notion that attachment of NEDD8 prevents cell death, genetic ablation of deneddylase 1 (DEN1) suppresses apoptosis. Unexpectedly, we find that Drosophila and human inhibitor of ap..
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Funding Acknowledgements
We would like to thank Millenium Pharmaceuticals for MLN4924 compound. We thank members of the Meier Lab for support and critical reading of the manuscript. In particular, we would like to thank Mariam Orme for advice with fly genetics, Markets Zvelebil for help with bioinformatics, and Helen Walden for support in structural information. M.B. is supported by a fellowship of the Deutsche Forschungsgemeinschaft and Breakthrough. We acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre.