Article
A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation.
Nature communications - 28 Sept 2023
Garnish Sarah E, Martin Katherine R, Kauppi Maria, Jackson Victoria E, Ambrose Rebecca, Eng Vik Ven, Chiou Shene, Meng Yanxiang, Frank Daniel, Tovey Crutchfield Emma C, Patel Komal M, Jacobsen Annette V, Atkin-Smith Georgia K, Di Rago Ladina, Doerflinger Marcel, Horne Christopher R, Hall Cathrine, Young Samuel N, Cook Matthew, Athanasopoulos Vicki, Vinuesa Carola G, Lawlor Kate E, Wicks Ian P, Ebert Gregor, Ng Ashley P, Slade Charlotte A, Pearson Jaclyn S, Samson André L, Silke John, Murphy James M, Hildebrand Joanne M
Abstract excerpt
Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132P in biological membranes and MLKLS132P overriding pharmacological and endogenous...
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