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Comment
. 2013 Sep 19;39(3):421-2.
doi: 10.1016/j.immuni.2013.08.020.

Pseudokiller, qu'est-ce que c'est?

Douglas R Green  1
Affiliations
Comment

Pseudokiller, qu'est-ce que c'est?

Douglas R Green. Immunity. .

Abstract

Necroptosis is mediated by engagement of RIP kinases and a downstream pseudokinase, MLKL. In this issue of Immunity, Murphy et al. (2013) show that it operates at or close to the final execution mechanism of the death process.

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Figures

Figure 1
Figure 1. MLKL acts downstream of RIPK3 in necroptosis
Ligation of death receptors or cell surface TLRs (via the adapter, TRIF) engage RIPK1, which then forms an amyloid-like complex with RIPK3. RIPK1 also recruits FADD, cFLIPL (FLIP) and caspase-8; the protease activity of the complex prevents necroptosis. Disruption or blockade of the protease activity allows the formation of the RIPK3 necrosome, which then phosphorylates MLKL. This probably induces MLKL “activation” via disruption of the K219-Q343 interaction in the pseudokinase domain. Active MLKL then promotes necroptosis and possibly other inflammatory events. (The author thanks Dr. Tudor Moldoveanu, who assisted with the image of the MLKL structure).
See this image and copyright information in PMC

Comment on

  • The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism.
    Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI, Young SN, Varghese LN, Tannahill GM, Hatchell EC, Majewski IJ, Okamoto T, Dobson RC, Hilton DJ, Babon JJ, Nicola NA, Strasser A, Silke J, Alexander WS. Murphy JM, et al. Immunity. 2013 Sep 19;39(3):443-53. doi: 10.1016/j.immuni.2013.06.018. Epub 2013 Sep 5. Immunity. 2013. PMID: 24012422

References

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