Journal article
Evolutionary divergence of the necroptosis effector MLKL
MC Tanzer, I Matti, JM Hildebrand, SN Young, A Wardak, A Tripaydonis, EJ Petrie, AL Mildenhall, DL Vaux, JE Vince, PE Czabotar, J Silke, JM Murphy
Cell Death and Differentiation | Published : 2016
DOI: 10.1038/cdd.2015.169
Abstract
The pseudokinase, MLKL (mixed-lineage kinase domain-like), is the most terminal obligatory component of the necroptosis cell death pathway known. Phosphorylation of the MLKL pseudokinase domain by the protein kinase, receptor interacting protein kinase-3 (RIPK3), is known to be the key step in MLKL activation. This phosphorylation event is believed to trigger a molecular switch, leading to exposure of the N-terminal four-helix bundle (4HB) domain of MLKL, its oligomerization, membrane translocation and ultimately cell death. To examine how well this process is evolutionarily conserved, we analysed the function of MLKL orthologues. Surprisingly, and unlike their mouse, horse and frog counterp..
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Awarded by State Government of Victoria
Funding Acknowledgements
We thank Professor Mark Hampton and Dr. Andreas Konigstorfer for kindly providing HT29 cells and Dr. Toru Okamoto for development of the inducible lentiviral vector. This work was supported by National Health and Medical Research Council of Australia (NHMRC) grants (461221, 1046010, 1051210, 1057888, 1057905, 1067289) and fellowships to JMH (541951), DLV (1020136), JEV (1052598), PEC (1079700) and JS (541901, 1058190); an Australian Research Council Future Fellowship to JMM (FT100100100); a Victorian International Research Scholarship to MCT; with additional support from the Victorian State Government Operational Infrastructure Support and NHMRC IRIISS grant (9000220).