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2. Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes

Author

Moschandrea, Chrysanthi, Kondylis, Vangelis, Evangelakos, Ioannis, Herholz, Marija, Schneider, Farina, Schmidt, Christina, Yang, Ming, Ehret, Sandra, Heine, Markus, Jaeckstein, Michelle Y., Szczepanowska, Karolina, Schwarzer, Robin, Baumann, Linda, Bock, Theresa, Nikitopoulou, Efterpi, Brodesser, Susanne, Krüger, Marcus, Frezza, Christian, Heeren, Joerg, Trifunovic, Aleksandra, and Pasparakis, Manolis

Published
2024
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5. Apoptotic cell death in disease—Current understanding of the NCCD 2023

Author

Vitale, Ilio, Pietrocola, Federico, Guilbaud, Emma, Aaronson, Stuart A., Abrams, John M., Adam, Dieter, Agostini, Massimiliano, Agostinis, Patrizia, Alnemri, Emad S., Altucci, Lucia, Amelio, Ivano, Andrews, David W., Aqeilan, Rami I., Arama, Eli, Baehrecke, Eric H., Balachandran, Siddharth, Bano, Daniele, Barlev, Nickolai A., Bartek, Jiri, Bazan, Nicolas G., Becker, Christoph, Bernassola, Francesca, Bertrand, Mathieu J. M., Bianchi, Marco E., Blagosklonny, Mikhail V., Blander, J. Magarian, Blandino, Giovanni, Blomgren, Klas, Borner, Christoph, Bortner, Carl D., Bove, Pierluigi, Boya, Patricia, Brenner, Catherine, Broz, Petr, Brunner, Thomas, Damgaard, Rune Busk, Calin, George A., Campanella, Michelangelo, Candi, Eleonora, Carbone, Michele, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chan, Francis K. -M., Chen, Guo-Qiang, Chen, Quan, Chen, Youhai H., Cheng, Emily H., Chipuk, Jerry E., Cidlowski, John A., Ciechanover, Aaron, Ciliberto, Gennaro, Conrad, Marcus, Cubillos-Ruiz, Juan R., Czabotar, Peter E., D’Angiolella, Vincenzo, Daugaard, Mads, Dawson, Ted M., Dawson, Valina L., De Maria, Ruggero, De Strooper, Bart, Debatin, Klaus-Michael, Deberardinis, Ralph J., Degterev, Alexei, Del Sal, Giannino, Deshmukh, Mohanish, Di Virgilio, Francesco, Diederich, Marc, Dixon, Scott J., Dynlacht, Brian D., El-Deiry, Wafik S., Elrod, John W., Engeland, Kurt, Fimia, Gian Maria, Galassi, Claudia, Ganini, Carlo, Garcia-Saez, Ana J., Garg, Abhishek D., Garrido, Carmen, Gavathiotis, Evripidis, Gerlic, Motti, Ghosh, Sourav, Green, Douglas R., Greene, Lloyd A., Gronemeyer, Hinrich, Häcker, Georg, Hajnóczky, György, Hardwick, J. Marie, Haupt, Ygal, He, Sudan, Heery, David M., Hengartner, Michael O., Hetz, Claudio, Hildeman, David A., Ichijo, Hidenori, Inoue, Satoshi, Jäättelä, Marja, Janic, Ana, Joseph, Bertrand, Jost, Philipp J., Kanneganti, Thirumala-Devi, Karin, Michael, Kashkar, Hamid, Kaufmann, Thomas, Kelly, Gemma L., Kepp, Oliver, Kimchi, Adi, Kitsis, Richard N., Klionsky, Daniel J., Kluck, Ruth, Krysko, Dmitri V., Kulms, Dagmar, Kumar, Sharad, Lavandero, Sergio, Lavrik, Inna N., Lemasters, John J., Liccardi, Gianmaria, Linkermann, Andreas, Lipton, Stuart A., Lockshin, Richard A., López-Otín, Carlos, Luedde, Tom, MacFarlane, Marion, Madeo, Frank, Malorni, Walter, Manic, Gwenola, Mantovani, Roberto, Marchi, Saverio, Marine, Jean-Christophe, Martin, Seamus J., Martinou, Jean-Claude, Mastroberardino, Pier G., Medema, Jan Paul, Mehlen, Patrick, Meier, Pascal, Melino, Gerry, Melino, Sonia, Miao, Edward A., Moll, Ute M., Muñoz-Pinedo, Cristina, Murphy, Daniel J., Niklison-Chirou, Maria Victoria, Novelli, Flavia, Núñez, Gabriel, Oberst, Andrew, Ofengeim, Dimitry, Opferman, Joseph T., Oren, Moshe, Pagano, Michele, Panaretakis, Theocharis, Pasparakis, Manolis, Penninger, Josef M., Pentimalli, Francesca, Pereira, David M., Pervaiz, Shazib, Peter, Marcus E., Pinton, Paolo, Porta, Giovanni, Prehn, Jochen H. M., Puthalakath, Hamsa, Rabinovich, Gabriel A., Rajalingam, Krishnaraj, Ravichandran, Kodi S., Rehm, Markus, Ricci, Jean-Ehrland, Rizzuto, Rosario, Robinson, Nirmal, Rodrigues, Cecilia M. P., Rotblat, Barak, Rothlin, Carla V., Rubinsztein, David C., Rudel, Thomas, Rufini, Alessandro, Ryan, Kevin M., Sarosiek, Kristopher A., Sawa, Akira, Sayan, Emre, Schroder, Kate, Scorrano, Luca, Sesti, Federico, Shao, Feng, Shi, Yufang, Sica, Giuseppe S., Silke, John, Simon, Hans-Uwe, Sistigu, Antonella, Stephanou, Anastasis, Stockwell, Brent R., Strapazzon, Flavie, Strasser, Andreas, Sun, Liming, Sun, Erwei, Sun, Qiang, Szabadkai, Gyorgy, Tait, Stephen W. G., Tang, Daolin, Tavernarakis, Nektarios, Troy, Carol M., Turk, Boris, Urbano, Nicoletta, Vandenabeele, Peter, Vanden Berghe, Tom, Vander Heiden, Matthew G., Vanderluit, Jacqueline L., Verkhratsky, Alexei, Villunger, Andreas, von Karstedt, Silvia, Voss, Anne K., Vousden, Karen H., Vucic, Domagoj, Vuri, Daniela, Wagner, Erwin F., Walczak, Henning, Wallach, David, Wang, Ruoning, Wang, Ying, Weber, Achim, Wood, Will, Yamazaki, Takahiro, Yang, Huang-Tian, Zakeri, Zahra, Zawacka-Pankau, Joanna E., Zhang, Lin, Zhang, Haibing, Zhivotovsky, Boris, Zhou, Wenzhao, Piacentini, Mauro, Kroemer, Guido, and Galluzzi, Lorenzo

Published
2023
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8. Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF.

Author

Hausmann, Annika, Felmy, Boas, Kunz, Leo, Kroon, Sanne, Berthold, Dorothée, Ganz, Giverny, Sandu, Ioana, Nakamura, Toshihiro, Zangger, Nathan, Zhang, Yang, Dolowschiak, Tamas, Fattinger, Stefan, Furter, Markus, Müller-Hauser, Anna, Barthel, Manja, Vlantis, Katerina, Wachsmuth, Laurens, Kisielow, Jan, Tortola, Luigi, Heide, Danijela, Heikenwälder, Mathias, Oxenius, Annette, Kopf, Manfred, Schroeder, Timm, Pasparakis, Manolis, Sellin, Mikael, and Hardt, Wolf-Dietrich

Subjects
Animals, Anti-Bacterial Agents, Epithelial Cells, Gene Expression Regulation, Inflammation, Intestinal Mucosa, Intestines, Macrophages, Mice, Mice, Inbred C57BL, NF-kappa B, Signal Transduction, Tumor Necrosis Factors
Abstract

Intestinal epithelial cell (IEC) NF-κB signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this balance and how bacterial exposure elicits the process. Pure LPS induces epithelial NF-κB activation in vivo. However, we found that in mice, IECs do not respond directly to LPS. Instead, tissue-resident lamina propria intercrypt macrophages sense LPS via TLR4 and rapidly secrete TNF to elicit epithelial NF-κB signaling in their immediate neighborhood. This response pattern is relevant also during oral enteropathogen infection. The macrophage-TNF-IEC axis avoids responses to luminal microbiota LPS but enables crypt- or tissue-scale epithelial NF-κB responses in proportion to the microbial threat. Thereby, intercrypt macrophages fulfill important sentinel functions as first responders to Gram-negative microbes breaching the epithelial barrier. The tunability of this crypt response allows the induction of defense mechanisms at an appropriate scale according to the localization and intensity of microbial triggers.

Published
2021

10. Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease

Author

Lalaoui, Najoua, Boyden, Steven E, Oda, Hirotsugu, Wood, Geryl M, Stone, Deborah L, Chau, Diep, Liu, Lin, Stoffels, Monique, Kratina, Tobias, Lawlor, Kate E, Zaal, Kristien JM, Hoffmann, Patrycja M, Etemadi, Nima, Shield-Artin, Kristy, Biben, Christine, Tsai, Wanxia Li, Blake, Mary D, Kuehn, Hye Sun, Yang, Dan, Anderton, Holly, Silke, Natasha, Wachsmuth, Laurens, Zheng, Lixin, Moura, Natalia Sampaio, Beck, David B, Gutierrez-Cruz, Gustavo, Ombrello, Amanda K, Pinto-Patarroyo, Gineth P, Kueh, Andrew J, Herold, Marco J, Hall, Cathrine, Wang, Hongying, Chae, Jae Jin, Dmitrieva, Natalia I, McKenzie, Mark, Light, Amanda, Barham, Beverly K, Jones, Anne, Romeo, Tina M, Zhou, Qing, Aksentijevich, Ivona, Mullikin, James C, Gross, Andrew J, Shum, Anthony K, Hawkins, Edwin D, Masters, Seth L, Lenardo, Michael J, Boehm, Manfred, Rosenzweig, Sergio D, Pasparakis, Manolis, Voss, Anne K, Gadina, Massimo, Kastner, Daniel L, and Silke, John

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Biodefense, Prevention, Rare Diseases, Vaccine Related, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Animals, Caspase 3, Caspase 8, Female, Hereditary Autoinflammatory Diseases, Humans, MAP Kinase Kinase Kinases, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Pedigree, Receptor-Interacting Protein Serine-Threonine Kinases, General Science & Technology
Abstract

RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it is thought to inhibit activation of RIPK3 and necroptosis8. Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and result in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy-a condition we term 'cleavage-resistant RIPK1-induced autoinflammatory syndrome'. To define the mechanism for this disease, we generated a cleavage-resistant Ripk1D325A mutant mouse strain. Whereas Ripk1-/- mice died postnatally from systemic inflammation, Ripk1D325A/D325A mice died during embryogenesis. Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3, but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1D325A/D325A embryonic lethality, although the mice died before weaning from multi-organ inflammation in a RIPK3-dependent manner. Consistently, Ripk1D325A/D325A and Ripk1D325A/+ cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1D325A/+ mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life.

Published
2020

11. RIPK1 Mediates TNF-Induced Intestinal Crypt Apoptosis During Chronic NF-κB Activation

Author

Wong, Jerry, Garcia-Carbonell, Ricard, Zelic, Matija, Ho, Samuel B, Boland, Brigid S, Yao, Shih-Jing, Desai, Shalin A, Das, Soumita, Planell, Núria, Harris, Philip A, Font-Burgada, Joan, Taniguchi, Koji, Bertin, John, Salas, Azucena, Pasparakis, Manolis, Gough, Pete J, Kelliher, Michelle, Karin, Michael, and Guma, Monica

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Autoimmune Disease, Inflammatory Bowel Disease, Crohn's Disease, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Adult, Animals, Apoptosis, Caspase 3, Cells, Cultured, Colitis, Ulcerative, Colon, Colonoscopy, Crohn Disease, Disease Models, Animal, Epithelial Cells, Gene Knock-In Techniques, Humans, I-kappa B Kinase, Ileum, Imidazoles, Indoles, Intestinal Mucosa, Mice, Knockout, Organoids, Primary Cell Culture, RNA-Seq, Receptor-Interacting Protein Serine-Threonine Kinases, Transcription Factor RelA, Tumor Necrosis Factor-alpha, IBD, RIPK1, Intestinal Epithelial Cell, Ripoptosome, Cell Death, Biochemistry and cell biology, Clinical sciences
Abstract

Background and aimsTumor necrosis factor (TNF) is a major pathogenic effector and a therapeutic target in inflammatory bowel disease (IBD), yet the basis for TNF-induced intestinal epithelial cell (IEC) death is unknown, because TNF does not kill normal IECs. Here, we investigated how chronic nuclear factor (NF)- κB activation, which occurs in human IBD, promotes TNF-dependent IEC death in mice.MethodsHuman IBD specimens were stained for p65 and cleaved caspase-3. C57BL/6 mice with constitutively active IKKβ in IEC (Ikkβ(EE)IEC), Ripk1D138N/D138N knockin mice, and Ripk3-/- mice were injected with TNF or lipopolysaccharide. Enteroids were also isolated from these mice and challenged with TNF with or without RIPK1 and RIPK3 inhibitors or butylated hydroxyanisole. Ripoptosome-mediated caspase-8 activation was assessed by immunoprecipitation.ResultsNF-κB activation in human IBD correlated with appearance of cleaved caspase-3. Congruently, unlike normal mouse IECs that are TNF-resistant, IECs in Ikkβ(EE)IEC mice and enteroids were susceptible to TNF-dependent apoptosis, which depended on the protein kinase function of RIPK1. Constitutively active IKKβ facilitated ripoptosome formation, a RIPK1 signaling complex that mediates caspase-8 activation by TNF. Butylated hydroxyanisole treatment and RIPK1 inhibitors attenuated TNF-induced and ripoptosome-mediated caspase-8 activation and IEC death in vitro and in vivo.ConclusionsContrary to common expectations, chronic NF-κB activation induced intestinal crypt apoptosis after TNF stimulation, resulting in severe mucosal erosion. RIPK1 kinase inhibitors selectively inhibited TNF destructive properties while preserving its survival and proliferative properties, which do not require RIPK1 kinase activity. RIPK1 kinase inhibition could be a potential treatment for IBD.

Published
2020

12. ADAR1 averts fatal type I interferon induction by ZBP1

Author

Jiao, Huipeng, Wachsmuth, Laurens, Wolf, Simone, Lohmann, Juliane, Nagata, Masahiro, Kaya, Göksu Gökberk, Oikonomou, Nikos, Kondylis, Vangelis, Rogg, Manuel, Diebold, Martin, Tröder, Simon E., Zevnik, Branko, Prinz, Marco, Schell, Christoph, Young, George R., Kassiotis, George, and Pasparakis, Manolis

Published
2022
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13. NIK/MAP3K14 in hepatocytes orchestrates NASH to hepatocellular carcinoma progression via JAK2/STAT5 inhibition

Author

Vesting, Anna Juliane, Jais, Alexander, Klemm, Paul, Steuernagel, Lukas, Wienand, Peter, Fog-Tonnesen, Morten, Hvid, Henning, Schumacher, Anna–Lena, Kukat, Christian, Nolte, Hendrik, Georgomanolis, Theodoros, Altmüller, Janine, Pasparakis, Manolis, Schmidt, Andreas, Krüger, Marcus, Supprian, Marc Schmidt, Waisman, Ari, Straub, Beate Katharina, Raschzok, Nathanael, Bernier, Michel, Birkenfeld, Andreas L., Hövelmeyer, Nadine, Brüning, Jens C., and Wunderlich, F. Thomas

Published
2022
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20. cIAPs control RIPK1 kinase activity‐dependent and ‐independent cell death and tissue inflammation

Author

Schorn, Fabian, primary, Werthenbach, J Paul, additional, Hoffmann, Mattes, additional, Daoud, Mila, additional, Stachelscheid, Johanna, additional, Schiffmann, Lars M, additional, Hildebrandt, Ximena, additional, Lyu, Su Ir, additional, Peltzer, Nieves, additional, Quaas, Alexander, additional, Vucic, Domagoj, additional, Silke, John, additional, Pasparakis, Manolis, additional, and Kashkar, Hamid, additional

Published
2023
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24. Lipid signalling drives proteolytic rewiring of mitochondria by YME1L

Author

MacVicar, Thomas, Ohba, Yohsuke, Nolte, Hendrik, Mayer, Fiona Carola, Tatsuta, Takashi, Sprenger, Hans-Georg, Lindner, Barbara, Zhao, Yue, Li, Jiahui, Bruns, Christiane, Krüger, Marcus, Habich, Markus, Riemer, Jan, Schwarzer, Robin, Pasparakis, Manolis, Henschke, Sinika, Brüning, Jens C., Zamboni, Nicola, and Langer, Thomas

Published
2019
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26. Oncogenic KRAS-induces necroptotic priming of pancreatic neoplasia

Author

Tishina, Sofya, primary, Dahlhaus, Alina, additional, Androulidaki, Ariadne, additional, Kotliar, Michael, additional, Mulalic, Lejla, additional, Rakhsh-Khorshid, Hassan, additional, Hocher, Florian, additional, Stroh, Jenny, additional, Beck, Julia, additional, Manik, Marta, additional, Williams, Riley, additional, Gülcüler, Gülce, additional, Abdallah, Ali, additional, Bebber, Christina, additional, Reese, Moritz, additional, Lim, Jonathan, additional, Trauzold, Anna, additional, Quaas, Alexander, additional, Brägelmann, Johannes, additional, Beleggia, Filippo, additional, Pasparakis, Manolis, additional, Liccardi, Gianmaria, additional, Balachandran, Siddharth, additional, Astsaturov, Igor, additional, and Von Karstedt, Silvia, additional

Published
2023
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27. Caspase 8 protects pancreatic neoplasia from KRAS-driven necroptotic priming

Author

Tishina, Sofya, primary, Dahlhaus, Alina, additional, Androulidaki, Ariadne, additional, Kotliar, Michael, additional, Mulalic, Lejla, additional, Rakhsh-Khorshid, Hassan, additional, Hocher, Florian, additional, Stroh, Jenny, additional, Beck, Julia, additional, Manik, Marta, additional, Williams, Riley, additional, Gülcüler, Gülce, additional, Abdallah, Ali, additional, Bebber, Christina, additional, Reese, Moritz, additional, Lim, Jonathan, additional, Trauzold, Anna, additional, Quaas, Alexander, additional, Brägelmann, Johannes, additional, Beleggia, Filippo, additional, Pasparakis, Manolis, additional, Liccardi, Gianmaria, additional, Balachandran, Siddharth, additional, Astsaturov, Igor, additional, and Von Karstedt, Silvia, additional

Published
2023
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29. Epithelial Cell Death and Inflammation in Skin

Author

Kumari, Snehlata, Pasparakis, Manolis, Compans, Richard W, Series editor, Honjo, Tasuku, Series editor, Oldstone, Michael B. A., Series editor, Vogt, Peter K., Series editor, Malissen, Bernard, Series editor, Aktories, Klaus, Series editor, Kawaoka, Yoshihiro, Series editor, Rappuoli, Rino, Series editor, Galan, Jorge E., Series editor, Ahmed, Rafi, Series editor, Palme, Klaus, Series editor, Casadevall, Arturo, Series editor, Garcia-Sastre, Adolfo, Series editor, Nagata, Shigekazu, editor, and Nakano, Hiroyasu, editor

Published
2017
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32. Data from IκB Kinase α Is Required for Development and Progression of KRAS-Mutant Lung Adenocarcinoma

Author

Vreka, Malamati, primary, Lilis, Ioannis, primary, Papageorgopoulou, Maria, primary, Giotopoulou, Georgia A., primary, Lianou, Marina, primary, Giopanou, Ioanna, primary, Kanellakis, Nikolaos I., primary, Spella, Magda, primary, Agalioti, Theodora, primary, Armenis, Vasileios, primary, Goldmann, Torsten, primary, Marwitz, Sebastian, primary, Yull, Fiona E., primary, Blackwell, Timothy S., primary, Pasparakis, Manolis, primary, Marazioti, Antonia, primary, and Stathopoulos, Georgios T., primary

Published
2023
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33. Supplementary Data from IκB Kinase α Is Required for Development and Progression of KRAS-Mutant Lung Adenocarcinoma

Author

Vreka, Malamati, primary, Lilis, Ioannis, primary, Papageorgopoulou, Maria, primary, Giotopoulou, Georgia A., primary, Lianou, Marina, primary, Giopanou, Ioanna, primary, Kanellakis, Nikolaos I., primary, Spella, Magda, primary, Agalioti, Theodora, primary, Armenis, Vasileios, primary, Goldmann, Torsten, primary, Marwitz, Sebastian, primary, Yull, Fiona E., primary, Blackwell, Timothy S., primary, Pasparakis, Manolis, primary, Marazioti, Antonia, primary, and Stathopoulos, Georgios T., primary

Published
2023
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39. RIP kinase 1-dependent endothelial necroptosis underlies systemic inflammatory response syndrome

Author

Zelic, Matija, Roderick, Justine E., O'Donnell, Joanne A., Lehman, Jesse, Lim, Sung Eun, Janardhan, Harish P., Trivedi, Chinmay M., Pasparakis, Manolis, and Kelliher, Michelle A.

Subjects
Apoptosis -- Health aspects, Tumor necrosis factor -- Health aspects, Inflammation -- Models -- Development and progression, Protein kinases -- Health aspects -- Physiological aspects, Sepsis -- Development and progression -- Care and treatment, Health care industry
Abstract

Receptor interacting protein kinase 1 (RIPK1) has important kinase-dependent and kinase-independent scaffolding functions that activate or prevent apoptosis or necroptosis in a cell context-dependent manner. The kinase activity of RIPK1 mediates hypothermia and lethality in a mouse model of TNF-induced shock, reflecting the hyperinflammatory state of systemic inflammatory response syndrome (SIRS), where the proinflammatory 'cytokine storm' has long been viewed as detrimental. Here, we demonstrate that cytokine and chemokine levels did not predict survival and, importantly, that kinase- inactive [Ripk1.sup.D138N/D138N] hematopoietic cells afforded little protection from TNF- or TNF/zVAD-induced shock in reconstituted mice. Unexpectedly, RIPK1 kinase-inactive mice transplanted with WT hematopoietic cells remained resistant to TNF-induced shock, revealing that a nonhematopoietic lineage mediated protection. TNF-treated [Ripk1.sup.D138N/D138N] mice exhibited no significant increases in intestinal or vascular permeability, nor did they activate the clotting cascade. We show that TNF administration damaged the liver vascular endothelium and induced phosphorylated mixed lineage kinase domain-like (phospho-MLKL) reactivity in endothelial cells isolated from TNF/zVAD-treated WT, but not [Ripk1.sup.D138N/D138N], mice. These data reveal that the tissue damage present in this SIRS model is reflected, in part, by breaks in the vasculature due to endothelial cell necroptosis and thereby predict that RIPK1 kinase inhibitors may provide clinical benefit to shock and/or sepsis patients., Introduction The serine/threonine receptor interacting protein kinase 1 (RIPK1) plays a prominent role in proinflammatory and cell-survival signaling by mediating optimal NF-[kappa]B and MAPK pathway activation downstream of TNF and [...]

Published
2018
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40. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Author

Galluzzi, Lorenzo, Vitale, Ilio, Aaronson, Stuart A., Abrams, John M., Adam, Dieter, Agostinis, Patrizia, Alnemri, Emad S., Altucci, Lucia, Amelio, Ivano, Andrews, David W., Annicchiarico-Petruzzelli, Margherita, Antonov, Alexey V., Arama, Eli, Baehrecke, Eric H., Barlev, Nickolai A., Bazan, Nicolas G., Bernassola, Francesca, Bertrand, Mathieu J. M., Bianchi, Katiuscia, Blagosklonny, Mikhail V., Blomgren, Klas, Borner, Christoph, Boya, Patricia, Brenner, Catherine, Campanella, Michelangelo, Candi, Eleonora, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chan, Francis K.-M., Chandel, Navdeep S., Cheng, Emily H., Chipuk, Jerry E., Cidlowski, John A., Ciechanover, Aaron, Cohen, Gerald M., Conrad, Marcus, Cubillos-Ruiz, Juan R., Czabotar, Peter E., D’Angiolella, Vincenzo, Dawson, Ted M., Dawson, Valina L., De Laurenzi, Vincenzo, De Maria, Ruggero, Debatin, Klaus-Michael, DeBerardinis, Ralph J., Deshmukh, Mohanish, Di Daniele, Nicola, Di Virgilio, Francesco, Dixit, Vishva M., Dixon, Scott J., Duckett, Colin S., Dynlacht, Brian D., El-Deiry, Wafik S., Elrod, John W., Fimia, Gian Maria, Fulda, Simone, García-Sáez, Ana J., Garg, Abhishek D., Garrido, Carmen, Gavathiotis, Evripidis, Golstein, Pierre, Gottlieb, Eyal, Green, Douglas R., Greene, Lloyd A., Gronemeyer, Hinrich, Gross, Atan, Hajnoczky, Gyorgy, Hardwick, J. Marie, Harris, Isaac S., Hengartner, Michael O., Hetz, Claudio, Ichijo, Hidenori, Jäättelä, Marja, Joseph, Bertrand, Jost, Philipp J., Juin, Philippe P., Kaiser, William J., Karin, Michael, Kaufmann, Thomas, Kepp, Oliver, Kimchi, Adi, Kitsis, Richard N., Klionsky, Daniel J., Knight, Richard A., Kumar, Sharad, Lee, Sam W., Lemasters, John J., Levine, Beth, Linkermann, Andreas, Lipton, Stuart A., Lockshin, Richard A., López-Otín, Carlos, Lowe, Scott W., Luedde, Tom, Lugli, Enrico, MacFarlane, Marion, Madeo, Frank, Malewicz, Michal, Malorni, Walter, Manic, Gwenola, Marine, Jean-Christophe, Martin, Seamus J., Martinou, Jean-Claude, Medema, Jan Paul, Mehlen, Patrick, Meier, Pascal, Melino, Sonia, Miao, Edward A., Molkentin, Jeffery D., Moll, Ute M., Muñoz-Pinedo, Cristina, Nagata, Shigekazu, Nuñez, Gabriel, Oberst, Andrew, Oren, Moshe, Overholtzer, Michael, Pagano, Michele, Panaretakis, Theocharis, Pasparakis, Manolis, Penninger, Josef M., Pereira, David M., Pervaiz, Shazib, Peter, Marcus E., Piacentini, Mauro, Pinton, Paolo, Prehn, Jochen H.M., Puthalakath, Hamsa, Rabinovich, Gabriel A., Rehm, Markus, Rizzuto, Rosario, Rodrigues, Cecilia M.P., Rubinsztein, David C., Rudel, Thomas, Ryan, Kevin M., Sayan, Emre, Scorrano, Luca, Shao, Feng, Shi, Yufang, Silke, John, Simon, Hans-Uwe, Sistigu, Antonella, Stockwell, Brent R., Strasser, Andreas, Szabadkai, Gyorgy, Tait, Stephen W.G., Tang, Daolin, Tavernarakis, Nektarios, Thorburn, Andrew, Tsujimoto, Yoshihide, Turk, Boris, Vanden Berghe, Tom, Vandenabeele, Peter, Vander Heiden, Matthew G., Villunger, Andreas, Virgin, Herbert W., Vousden, Karen H., Vucic, Domagoj, Wagner, Erwin F., Walczak, Henning, Wallach, David, Wang, Ying, Wells, James A., Wood, Will, Yuan, Junying, Zakeri, Zahra, Zhivotovsky, Boris, Zitvogel, Laurence, Melino, Gerry, and Kroemer, Guido

Published
2018
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43. B-cell–specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice

Author

Knittel, Gero, Liedgens, Paul, Korovkina, Darya, Seeger, Jens M., Al-Baldawi, Yussor, Al-Maarri, Mona, Fritz, Christian, Vlantis, Katerina, Bezhanova, Svetlana, Scheel, Andreas H., Wolz, Olaf-Oliver, Reimann, Maurice, Möller, Peter, López, Cristina, Schlesner, Matthias, Lohneis, Philipp, Weber, Alexander N.R., Trümper, Lorenz, Staudt, Louis M., Ortmann, Monika, Pasparakis, Manolis, Siebert, Reiner, Schmitt, Clemens A., Klatt, Andreas R., Wunderlich, F.Thomas, Schäfer, Stephan C., Persigehl, Thorsten, Montesinos-Rongen, Manuel, Odenthal, Margarete, Büttner, Reinhard, Frenzel, Lukas P., Kashkar, Hamid, and Reinhardt, H.Christian

Published
2016
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45. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS

Author

Ito, Yasushi, Ofengeim, Dimitry, Najafov, Ayaz, Das, Sudeshna, Saberi, Shahram, Li, Ying, Hitomi, Junichi, Zhu, Hong, Chen, Hongbo, Mayo, Lior, Geng, Jiefei, Amin, Palak, DeWitt, Judy Park, Mookhtiar, Adnan Kasim, Florez, Marcus, Ouchida, Amanda Tomie, Fan, Jian-bing, Pasparakis, Manolis, Kelliher, Michelle A., Ravits, John, and Yuan, Junying

Published
2016

48. Inhibition of MLKL impairs abdominal aortic aneurysm development by attenuating smooth muscle cell necroptosis

Author

Nemade, Harshal N, primary, Mehrkens, Dennis, additional, Lottermoser, Hannah Sophia, additional, Yilmaz, Zeynep Ece, additional, Schelemei, Patrick, additional, Picard, Felix Ruben, additional, Geißen, Simon, additional, Schwab, Gülsah Fülgen, additional, Hoyer, Friedrich Felix, additional, Guthoff, Henning, additional, Hof, Alexander, additional, Nettersheim, Felix Sebastian, additional, Sachinidis, Agapios, additional, Winkels, Holger, additional, Baldus, Stefan, additional, Pasparakis, Manolis, additional, Adam, Matti, additional, and Mollenhauer, Martin, additional

Published
2022
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49. Kinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis

Author

Van, Trieu-My, Polykratis, Apostolos, Straub, Beate Katharina, Kondylis, Vangelis, Papadopoulou, Nikoletta, and Pasparakis, Manolis

Subjects
Liver cancer -- Genetic aspects -- Development and progression -- Care and treatment, Phosphotransferases -- Health aspects, Cellular signal transduction -- Genetic aspects -- Health aspects, Health care industry
Abstract

The mechanisms that regulate cell death and inflammation play an important role in liver disease and cancer. Receptor-interacting protein kinase 1 (RIPK1) induces apoptosis and necroptosis via kinase-dependent mechanisms and exhibits kinase-independent prosurvival and proinflammatory functions. Here, we have used genetic mouse models to studythe role of RIPK1 in liver homeostasis, injury, and cancer. While ablating either RIPK1 or RelA in liver parenchymal cells (LPCs) did not cause spontaneous liver pathology, mice with combined deficiency of RIPK1 and RelA in LPCs showed increased hepatocyte apoptosis and developed spontaneous chronic liver disease and cancer that were independent of TNF receptor 1 (TNFR1) signaling. In contrast, mice with LPC-specific knockout of RIPK1 showed reduced diethylnitrosamine-induced (DEN-induced) livertumorigenesis that correlated with increased DEN-induced hepatocyte apoptosis. Lack of RIPK1 kinase activity did not inhibit DEN-induced liver tumor formation, showingthat kinase-independent functions of RIPK1 promote DEN-induced hepatocarcinogenesis. Moreover, mice lacking both RIPK1 and TNFR1 in LPCs displayed normal tumor formation in response to DEN, demonstrating that RIPK1 deficiency decreases DEN-induced livertumor formation in a TNFR1-dependent manner. Therefore, these findings indicate that RIPIO cooperates with NF-[kappa]B signaling to prevent TNFR1-independent hepatocyte apoptosis and the development of chronic liver disease and cancer, but acts downstream of TNFR1 signaling to promote DEN-induced liver tumorigenesis., Introduction Liver injury in response to immune deregulation and/or infection can result in acute liver failure or chronic liver disease. Chronic hepatocyte death coupled with compensatory hepatocyte proliferation greatly increases [...]

Published
2017
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50. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation

Author

Lin, Juan, Kumari, Snehlata, Kim, Chun, Van, Trieu-My, Wachsmuth, Laurens, Polykratis, Apostolos, and Pasparakis, Manolis

Subjects
Inflammation -- Development and progression -- Prevention, Necrosis -- Development and progression -- Prevention, Protein kinases -- Health aspects, Binding proteins -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Juan Lin [1]; Snehlata Kumari [1]; Chun Kim [1]; Trieu-My Van [1]; Laurens Wachsmuth [1]; Apostolos Polykratis [1]; Manolis Pasparakis (corresponding author) [1] Receptor-interacting protein kinase 1 (RIPK1) regulates [...]

Published
2016
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