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Necroptosis is preceded by nuclear translocation of the signaling proteins that induce it.

Cell death and differentiation (2015-07-18)
S Yoon, K Bogdanov, A Kovalenko, D Wallach
ABSTRACT

A signaling pathway that induces programmed necrotic cell death (necroptosis) was reported to be activated in cells by several cytokines and various pathogen components. The major proteins participating in that pathway are the protein kinases RIPK1 and RIPK3 and the pseudokinase mixed lineage kinase domain-like protein (MLKL). Recent studies have suggested that MLKL, once activated, mediates necroptosis by binding to cellular membranes, thereby triggering ion fluxes. However, our knowledge of both the sequence of molecular events leading to MLKL activation and the subcellular sites of these events is fragmentary. Here we report that the association of MLKL with the cell membrane in necroptotic death is preceded by the translocation of phosphorylated MLKL, along with RIPK1 and RIPK3, to the nucleus.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Triton X-114, laboratory grade
Sigma-Aldrich
Anti-MLKL (58-70) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Amyloid Protein Non-Aβ Component, ≥80% (HPLC)