Results 11 to 20 of about 12,009 (206)

HSP70 promotes MLKL polymerization and necroptosis [PDF]

Molecular & Cellular Oncology, 2020
Mixed lineage kinase domain-like protein (MLKL) is the proposed executioner of necroptosis. Our recent findings identify a novel inhibitor necroptosis-blocking compound 1 (NBC1) which specifically conjugates to two cysteines of heat shock protein 70 ...
Andrea N. Johnston, Zhigao Wang
doaj   +5 more sources

PROTACs Targeting MLKL Protect Cells from Necroptosis [PDF]

Journal of Medicinal Chemistry, 2023
Mixed Lineage Kinase domain-Like pseudokinase (MLKL) is implicated in a broad range of diseases due to its role as the ultimate effector of necroptosis and has therefore emerged as an attractive drug target. Here, we describe the development of PROteolysis TArgeting Chimeras (PROTACs) as a novel approach to knock down MLKL through chemical means.
Oliver H. Rathje, Lara Perryman, Richard J. Payne, Dieter W. Hamprecht   +3 more
core   +5 more sources

Macrophage‐derived MLKL in alcohol‐associated liver disease: Regulation of phagocytosis [PDF]

Hepatology, EarlyView., 2022
EtOH causes leaky gut allowing bacteria and PAMPs into the liver, resulting in hepatic inflammation and injury. We demonstrate that LPS induces STAT1‐mediated expression and phosphorylation of MLKL in macrophages and identify a novel function that myeloid MLKL translocates to phagosomes and lysosomes and regulates phagocytosis, which contributes to the
Xiaoqin Wu, Xiude Fan, Megan R. McMullen, Tatsunori Miyata, Adam Kim, Vai Pathak, Jianguo Wu, Le Z. Day, Josiah E. Hardesty, Nicole Welch, Jaividhya Dasarathy, Daniela S. Allende, Arthur J. McCullough, Jon M. Jacobs, Daniel M. Rotroff, Srinivasan Dasarathy, Laura E. Nagy   +16 more
wiley   +3 more sources

MLKL in cancer: more than a necroptosis regulator [PDF]

Cell Death & Differentiation, 2021
Mixed lineage kinase domain-like protein (MLKL) emerged as executioner of necroptosis, a RIPK3-dependent form of regulated necrosis. Cell death evasion is one of the hallmarks of cancer. Besides apoptosis, some cancers suppress necroptosis-associated mechanisms by for example epigenetic silencing of RIPK3 expression.
Sofie Martens, Jolien Bridelance, Ria Roelandt, Peter Vandenabeele, Nozomi Takahashi   +4 more
openaire   +3 more sources

Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice [PDF]

OncoImmunology, 2020
Vaccinia viruses (VACV) are a novel class of immune-oncolytic therapeutics and their mechanism of action is based both on their capacity to replicate selectively in cancer cells and to elicit danger signals that can boost anti-tumor immunity. We recently
Lien Van Hoecke, Stephanie Riederer, Xavier Saelens, Gerd Sutter, Juan J. Rojas   +4 more
doaj   +2 more sources

Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis [PDF]

Nature Communications, 2021
Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal ...
Sarah E. Garnish, Yanxiang Meng, Akiko Koide, Jarrod J. Sandow, Eric Denbaum, Annette V. Jacobsen, Wayland Yeung, Andre L. Samson, Christopher R. Horne, Cheree Fitzgibbon, Samuel N. Young, Phoebe P. C. Smith, Andrew I. Webb, Emma J. Petrie, Joanne M. Hildebrand, Natarajan Kannan, Peter E. Czabotar, Shohei Koide, James M. Murphy   +18 more
doaj   +2 more sources

Interferons Transcriptionally Up-Regulate MLKL Expression in Cancer Cells [PDF]

Neoplasia: An International Journal for Oncology Research, 2019
Interferons (IFNs) are key players in the tumor immune response and act by inducing the expression of IFN-stimulated genes (ISGs). Here, we identify the mixed-lineage kinase domain-like pseudokinase (MLKL) as an ISG in various cancer cell lines.
Anne-Kathrin Knuth, Stefanie Rösler, Barbara Schenk, Lisa Kowald, Sjoerd J.L. van Wijk, Simone Fulda   +5 more
doaj   +2 more sources

MLKL Compromises Plasma Membrane Integrity by Binding to Phosphatidylinositol Phosphates [PDF]

Cell Reports, 2014
Although mixed lineage kinase domain-like (MLKL) protein has emerged as a specific and crucial protein for necroptosis induction, how MLKL transduces the death signal remains poorly understood. Here, we demonstrate that the full four-helical bundle domain (4HBD) in the N-terminal region of MLKL is required and sufficient to induce its oligomerization ...
Dondelinger Yves, Declercq Wim, Montessuit Sylvie, Roelandt Ria, Goncalves Amanda, Bruggeman Inge, Hulpiau Paco, Weber Kathrin, Sehon Clark A, Marquis Robert W, Bertin John, Gough Peter J, Savvides Savvas, Martinou Jean-Claude, Bertrand Mathieu J M, Vandenabeele Peter   +15 more
openaire   +7 more sources

A RIPK3-independent role of MLKL in suppressing parthanatos promotes immune evasion in hepatocellular carcinoma [PDF]

Cell Discovery, 2023
Mixed lineage kinase domain-like (MLKL) is widely accepted as an executioner of necroptosis, in which MLKL mediates necroptotic signaling and triggers cell death in a receptor-interacting protein kinase 3 (RIPK3)-dependent manner.
Xifei Jiang, Wenjia Deng, Siyao Tao, Zheng Tang, Yuehong Chen, Mengxin Tian, Ting Wang, Chenyang Tao, Yize Li, Yuan Fang, Congying Pu, Jun Gao, Xiaomin Wang, Weifeng Qu, Xiameng Gai, Zhenbin Ding, Yixian Fu, Ying Zheng, Siyuwei Cao, Jian Zhou, Min Huang, Weiren Liu, Jun Xu, Jia Fan, Yinghong Shi   +24 more
doaj   +2 more sources

Flicking the molecular switch underlying MLKL-mediated necroptosis [PDF]

Molecular & Cellular Oncology, 2015
The pseudokinase domain of the necroptosis effector mixed lineage kinase domain-like (MLKL) functions as a latch to restrain the unleashing of its N-terminal 4-helix bundle (4HB) domain. Cell death mediated by the 4HB domain relies on membrane association and oligomerization, which can be inhibited by an ATP-mimetic small molecule that binds the ...
Hildebrand, JM, Lucet, IS, Murphy, JM
openaire   +6 more sources