A tale of two domains - a structural perspective of the pseudokinase, MLKL
- Author(s)
- Czabotar, PE; Murphy, JM;
- Details
- Publication Year 2015-09-03,Volume 282,Issue #22,Page 4268-4278
- Journal Title
- FEBS J
- Publication Type
- Journal Article
- Abstract
- Recently, the programmed necrosis or "necroptosis" cell death pathway has attracted much interest because of its implication in multiple pathologies, including inflammatory diseases and the cell death arising from ischemia reperfusion injuries. Pharmacologically, necroptosis is an attractive target, because, unlike the counterpart pathway, apoptosis, it is dispensable for mammalian development. In particular, the most terminal-known obligate effector in the necroptosis pathway, the pseudokinase MLKL (mixed lineage kinase domain-like), holds particular appeal because, thus far, its only known function is as a mediator of necroptotic cell death. Here, we review the current understanding and gaps in knowledge relating to how MLKL can be activated by RIPK3 downstream of TNF receptor 1:RIPK1, Toll like receptor-3:TRIF and viral DNA:DAI/ZBF1. We also discuss the potential mechanism(s) by which MLKL induces necroptotic cell death, with particular emphasis on insights arising from structural studies of mouse and human MLKL. This article is protected by copyright. All rights reserved.
- Publisher
- Wiley
- Research Division(s)
- Cell Signalling And Cell Death; Structural Biology
- PubMed ID
- 26337687
- Publisher's Version
- https://doi.org/10.1111/febs.13504
- NHMRC Grants
- NHMRC/637342, NHMRC/1057905, NHMRC/1067289,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-09-24 02:12:22
Last Modified: 2017-12-11 04:30:20