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Necrosome core machinery: MLKL
Cellular and Molecular Life Sciences, 2016In the study of regulated cell death, the rapidly expanding field of regulated necrosis, in particular necroptosis, has been drawing much attention. The signaling of necroptosis represents a sophisticated form of a death pathway. Anti-caspase mechanisms (e.g., using inhibitors of caspases, or genetic ablation of caspase-8) switch cell fate from ...
Jing, Zhang +3 more
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MLKL activity requires a splicing-regulated, druggable intramolecular interaction [PDF]
Molecular CellNecroptosis is an inflammatory form of regulated cell death implicated in a range of human pathologies, whose execution depends on the poorly understood pseudokinase mixed lineage kinase domain-like (MLKL).
Ana J García-Sáez +2 more
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MLKL Requires the Inositol Phosphate Code to Execute Necroptosis [PDF]
Molecular Cell, 2018 Necroptosis is an important form of lytic cell death triggered by injury and infection, but whether mixed lineage kinase domain-like (MLKL) is sufficient to execute this pathway is unknown. In a genetic selection for human cell mutants defective for MLKL-dependent necroptosis, we identified mutations in IPMK and ITPK1, which encode inositol phosphate ...
Scott Dixon +2 more
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MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis
Proceedings of the National Academy of Sciences of the United States of America, 2017 Mixed-lineage kinase domain-like protein (MLKL) is essential for TNF-α-induced necroptosis. How MLKL promotes cell death is still under debate. Here we report that MLKL forms SDS-resistant, disulfide bond-dependent polymers during necroptosis in both ...
Zhigao Wang, Shuzhen Liu
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TAM Kinases Promote Necroptosis by Regulating Oligomerization of MLKL [PDF]
Molecular Cell, 2019 Necroptosis, a cell death pathway mediated by the RIPK1-RIPK3-MLKL signaling cascade downstream of tumor necrosis factor α (TNF-α), has been implicated in many inflammatory diseases. Members of the TAM (Tyro3, Axl, and Mer) family of receptor tyrosine kinases are known for their anti-apoptotic, oncogenic, and anti-inflammatory roles.
Ayaz Najafov +2 more
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Science Signaling, 2019
TAM family kinases promote necroptosis by stimulating the phosphorylation and oligomerization of the pseudokinase MLKL.
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TAM family kinases promote necroptosis by stimulating the phosphorylation and oligomerization of the pseudokinase MLKL.
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Experimental Cell Research
The dimerization of the MLKL kinase-like domain (KLD) is a crucial step for MLKL activation in necroptosis. In 2014, it was discovered that GW806742X can directly bind to the mouse MLKL KLD via surface plasmon resonance (SPR) (Kd = 9.3 μM), inhibiting TNF-induced membrane translocation of MLKL and necroptosis.
Huayi Wang
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The dimerization of the MLKL kinase-like domain (KLD) is a crucial step for MLKL activation in necroptosis. In 2014, it was discovered that GW806742X can directly bind to the mouse MLKL KLD via surface plasmon resonance (SPR) (Kd = 9.3 μM), inhibiting TNF-induced membrane translocation of MLKL and necroptosis.
Huayi Wang
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Detection of MLKL Oligomerization During Programmed Necrosis
2018Programmed necrosis, also known as necroptosis, is a form of regulated necrotic cell death that is mediated by receptor-interacting protein kinases RIP1 (or RIPK1), RIP3 (or RIPK3), and the mixed lineage kinase domain-like protein, MLKL. Following the induction of programmed necrosis, MLKL is phosphorylated by RIP3 and oligomerizes and then the protein
Zhenyu, Cai, Zheng-Gang, Liu
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A patent review of MLKL modulators (2023 – present)
Expert Opinion on Therapeutic PatentsMixed-spectrum kinase structural domain-like protein (MLKL), which emerged as a pivotal regulator in biomedical research, plays a critical role in necroptotic pathways. Recent advancements have underscored the therapeutic potential of MLKL modulators.This review focuses on the patent literature covering MLKL-targeted molecules published from 2023 to ...
Bo-Wen Wan +2 more
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Insane in the membrane: a structural perspective of MLKL function in necroptosis
Immunology & Cell Biology, 2017Necroptosis (or ‘programmed necrosis’) is a caspase‐independent cell death pathway that operates downstream of death receptors, including Tumour Necrosis Factor Receptor‐1 (TNFR1), and the Toll‐like receptors, TLR3 and TLR4. Owing to its immunogenicity, necroptosis has been attributed roles in the pathogenesis of several diseases, including ...
Emma J, Petrie +2 more
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