Journal ArticleDOI
Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death
Dimitry Ofengeim,Junying Yuan +1 more
TLDR
The modification of RIP1 may provide a unique 'ubiquitin code' that determines whether a cell activates nuclear factor-κB to promote inflammatory signalling or induces cell death by apoptosis or necroptosis.Abstract:
Receptor-interacting protein 1 (RIP1) kinase has emerged as a key upstream regulator that controls inflammatory signalling as well as the activation of multiple cell death pathways, including apoptosis and necroptosis. The ability of RIP1 to modulate these key cellular events is tightly controlled by ubiquitylation, deubiquitylation and the interaction of RIP1 with a class of ubiquitin receptors. The modification of RIP1 may thus provide a unique 'ubiquitin code' that determines whether a cell activates nuclear factor-κB (NF-κB) to promote inflammatory signalling or induces cell death by apoptosis or necroptosis. Targeting RIP1 might be a novel therapeutic strategy for the treatment of both acute and chronic human diseases.read more
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Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
José Pedro Friedmann Angeli,Manuela Schneider,Bettina Proneth,Yulia Y. Tyurina,Vladimir A. Tyurin,Victoria Jayne Hammond,Nadja Herbach,Michaela Aichler,Axel Walch,E. Eggenhofer,Devaraj Basavarajappa,Olof Rådmark,Sho Kobayashi,Tobias Seibt,Heike Beck,Frauke Neff,Irene Esposito,Rüdiger Wanke,Heidi Förster,Olena Yefremova,Marc Heinrichmeyer,Georg W. Bornkamm,Edward K. Geissler,Stephen B. Thomas,Brent R. Stockwell,Valerie B. O'Donnell,Valerian E. Kagan,Joel A. Schick,Marcus Conrad +28 more
TL;DR: It is demonstrated that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection.
Journal ArticleDOI
Old, new and emerging functions of caspases.
TL;DR: Caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging, and some of these less studied and emerging functions of mammalian caspases are focused on.
Journal ArticleDOI
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target
Robert T. Manguso,Robert T. Manguso,Hans W. Pope,Hans W. Pope,Margaret D. Zimmer,Margaret D. Zimmer,Flavian D. Brown,Kathleen B. Yates,Kathleen B. Yates,Brian C. Miller,Brian C. Miller,Natalie B. Collins,Natalie B. Collins,Natalie B. Collins,Kevin Bi,Kevin Bi,Martin W. LaFleur,Vikram R. Juneja,Sarah A. Weiss,Jennifer A. Lo,David E. Fisher,Diana Miao,Diana Miao,Eliezer M. Van Allen,Eliezer M. Van Allen,David E. Root,Arlene H. Sharpe,Arlene H. Sharpe,John G. Doench,W. Nicholas Haining,W. Nicholas Haining,W. Nicholas Haining +31 more
TL;DR: Deletion of the protein tyrosine phosphatase PTPN2 in tumour cells increased the efficacy of immunotherapy by enhancing interferon-γ-mediated effects on antigen presentation and growth suppression, and a pooled in vivo genetic screening approach using CRISPR–Cas9 genome editing is used to discover previously undescribed immunotherapy targets.
Journal ArticleDOI
Apoptosis, autophagy, necroptosis, and cancer metastasis
TL;DR: This review summarizes the recent advances in the understanding of the mechanisms by which key regulators of apoptosis, autophagy, and necroptosis participate in cancer metastasis and discusses the crosstalk between apoptosis-autophagy-and-novoptosis involved in the regulation of cancer metastatic processes.
Journal ArticleDOI
Targeting Tumor-Associated Macrophages in Cancer.
TL;DR: Clinical trials with therapeutic agents that promote phagocytosis or suppress survival, proliferation, trafficking, or polarization of TAMs are currently underway, and early results offer the promise of improved cancer outcomes.
References
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Journal ArticleDOI
Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes
Olivier Micheau,Jürg Tschopp +1 more
TL;DR: TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal fails to be activated, and the cell survives.
Journal ArticleDOI
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Alexei Degterev,Zhihong Huang,Michael Boyce,Yaqiao Li,Prakash Jagtap,Noboru Mizushima,Gregory D. Cuny,Timothy J. Mitchison,Michael A. Moskowitz,Junying Yuan +9 more
TL;DR: It is demonstrated that necroptosis contributes to delayed mouse ischemic brain injury in vivo through a mechanism distinct from that of apoptosis and offers a new therapeutic target for stroke with an extended window for neuroprotection.
Journal ArticleDOI
TAK1 is a ubiquitin-dependent kinase of MKK and IKK
TL;DR: The purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism, indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK.
Journal ArticleDOI
Phosphorylation-Driven Assembly of the RIP1-RIP3 Complex Regulates Programmed Necrosis and Virus-Induced Inflammation
Young Sik Cho,Sreerupa Challa,David Moquin,Ryan M.J. Genga,Tathagat Dutta Ray,Melissa J. Guildford,Francis Ka-Ming Chan +6 more
TL;DR: The findings suggest that RIP3 controls programmed necrosis by initiating the pronecrotic kinase cascade, and that this is necessary for the inflammatory response against virus infections.