Journal article

The regulation of necroptosis by post-translational modifications

Yanxiang Meng, Jarrod J Sandow, Peter E Czabotar, James M Murphy

CELL DEATH AND DIFFERENTIATION | SPRINGERNATURE | Published : 2021

Abstract

Necroptosis is a caspase-independent, lytic form of programmed cell death whose errant activation has been widely implicated in many pathologies. The pathway relies on the assembly of the apical protein kinases, RIPK1 and RIPK3, into a high molecular weight cytoplasmic complex, termed the necrosome, downstream of death receptor or pathogen detector ligation. The necrosome serves as a platform for RIPK3-mediated phosphorylation of the terminal effector, the MLKL pseudokinase, which induces its oligomerization, translocation to, and perturbation of, the plasma membrane to cause cell death. Over the past 10 years, knowledge of the post-translational modifications that govern RIPK1, RIPK3 and ML..

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Grants

Awarded by Australian National Health and Medical Research Council


Funding Acknowledgements

We are grateful for scholarship support for YM (Melbourne Research Scholarship and AINSE PGRA scholarship) and thank the Australian National Health and Medical Research Council for fellowship (PEC, 1079700; JMM, 1172929), grant (1124735, 1124737), and infrastructure (IRIISS 9000587) support, with additional support from the Victorian Government Operational Infrastructure Support scheme.