Nature Communications (Jun 2021)
Ubiquitylation of MLKL at lysine 219 positively regulates necroptosis-induced tissue injury and pathogen clearance
- Laura Ramos Garcia,
- Tencho Tenev,
- Richard Newman,
- Rachel O. Haich,
- Gianmaria Liccardi,
- Sidonie Wicky John,
- Alessandro Annibaldi,
- Lu Yu,
- Mercedes Pardo,
- Samuel N. Young,
- Cheree Fitzgibbon,
- Winnie Fernando,
- Naomi Guppy,
- Hyojin Kim,
- Lung-Yu Liang,
- Isabelle S. Lucet,
- Andrew Kueh,
- Ioannis Roxanis,
- Patrycja Gazinska,
- Martin Sims,
- Tomoko Smyth,
- George Ward,
- John Bertin,
- Allison M. Beal,
- Brad Geddes,
- Jyoti S. Choudhary,
- James M. Murphy,
- K. Aurelia Ball,
- Jason W. Upton,
- Pascal Meier
Affiliations
- Laura Ramos Garcia
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Tencho Tenev
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Richard Newman
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Rachel O. Haich
- Department of Biological Sciences, Auburn University
- Gianmaria Liccardi
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Sidonie Wicky John
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Alessandro Annibaldi
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Lu Yu
- Functional Proteomics Group, The Institute of Cancer Research
- Mercedes Pardo
- Functional Proteomics Group, The Institute of Cancer Research
- Samuel N. Young
- Walter and Eliza Hall Institute of Medical Research
- Cheree Fitzgibbon
- Walter and Eliza Hall Institute of Medical Research
- Winnie Fernando
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Naomi Guppy
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Hyojin Kim
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Lung-Yu Liang
- Walter and Eliza Hall Institute of Medical Research
- Isabelle S. Lucet
- Walter and Eliza Hall Institute of Medical Research
- Andrew Kueh
- Walter and Eliza Hall Institute of Medical Research
- Ioannis Roxanis
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Patrycja Gazinska
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- Martin Sims
- Astex Pharmaceuticals
- Tomoko Smyth
- Astex Pharmaceuticals
- George Ward
- Astex Pharmaceuticals
- John Bertin
- Innate Immunity Research Unit, GlaxoSmithKline
- Allison M. Beal
- Innate Immunity Research Unit, GlaxoSmithKline
- Brad Geddes
- Innate Immunity Research Unit, GlaxoSmithKline
- Jyoti S. Choudhary
- Functional Proteomics Group, The Institute of Cancer Research
- James M. Murphy
- Walter and Eliza Hall Institute of Medical Research
- K. Aurelia Ball
- Department of Chemistry, Skidmore College
- Jason W. Upton
- Department of Biological Sciences, Auburn University
- Pascal Meier
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research
- DOI
- https://doi.org/10.1038/s41467-021-23474-5
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 18
Abstract
Necroptosis is a form of cell death characterized by membrane rupture via MLKL oligomerization, although mechanistic details remain unclear. Here, the authors show that MLKL ubiquitylation of K219 facilitates high-order membrane assembly and subsequent rupture, promoting cytotoxicity.
