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https://www.readbyqxmd.com/read/29142064/the-resurrection-of-the-piddosome-emerging-roles-in-the-dna-damage-response-and-centrosome-surveillance
#1
REVIEW
Valentina Sladky, Fabian Schuler, Luca L Fava, Andreas Villunger
The PIDDosome is often used as the alias for a multi-protein complex that includes the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the pro-form of an endopeptidase belonging to the caspase family, i.e. caspase-2. Yet, PIDD1 variants can also interact with a number of other proteins that include RIPK1 (also known as RIP1) and IKBKG (also known as NEMO), PCNA and RFC5, as well as nucleolar components such as NPM1 or NCL. This promiscuity in protein binding is facilitated mainly by autoprocessing of the full-length protein into various fragments that contain different structural domains...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29137405/necroptosis-regulated-proteins-expression-is-an-early-prognostic-biomarker-in-patient-with-sepsis-a-prospective-observational-study
#2
Bing Wang, Jian Li, Hong-Mei Gao, Ying-Hong Xing, Zhu Lin, Hong-Jie Li, Yong-Qiang Wang
Background and aim: Increasing researchers indicate that necroptosis is playing an important role in the regulation of systemic inflammatory response syndrome. The current study was to investigate the prognostic biomarker of the regulated proteins of necroptosis in sepsis patients. Results: One hundred and twenty-four patients were divided into three groups: 43 patients (34.68%) with sepsis, 39 patients (31.45%) with severe sepsis, and 42 patients (33.87%) with septic shock...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29123466/neuroprotective-effect-of-%C3%AE-caryophyllene-on-cerebral-ischemia-reperfusion-injury-via-regulation-of-necroptotic-neuronal-death-and-inflammation-in-vivo-and-in-vitro
#3
Mei Yang, Yongjiu Lv, Xiaocui Tian, Jie Lou, Ruidi An, Qian Zhang, Minghang Li, Lu Xu, Zhi Dong
Necrotic cell death is a hallmark feature of ischemic stroke and it may facilitate inflammation by releasing intracellular components after cell-membrane rupture. Previous studies reported that β-caryophyllene (BCP) mitigates cerebral ischemia-reperfusion (I/R) injury, but the underlying mechanism remains unclear. We explored whether BCP exerts a neuroprotective effect in cerebral I/R injury through inhibiting necroptotic cell death and inflammation. Primary neurons with and without BCP (0.2, 1, 5, 25 μM) treatment were exposed to oxygen-glucose deprivation and re-oxygenation (OGD/R)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29104146/mlkl-pitp%C3%AE-signaling-mediated-necroptosis-contributes-to-cisplatin-triggered-cell-death-in-lung-cancer-a549-cells
#4
Lin Jing, Fei Song, Zhenyu Liu, Jianghua Li, Bo Wu, Zhiguang Fu, Jianli Jiang, Zhinan Chen
Necroptosis has been reported to be involved in cisplatin-induced cell death, but the mechanisms underlying the occurrence of necroptosis are not fully elucidated. In this study, we show that apart from apoptosis, cisplatin induces necroptosis in A549 cells. The alleviation of cell death by two necroptosis inhibitors-necrostatin-1 (Nec-1) and necrosulfonamide (NSA), and the phosphorylation of mixed lineage kinase domain-like protein (MLKL) at serine 358, suggest the involvement of receptor-interacting protein kinase 1 (RIPK1)-RIPK3-MLKL signaling in cisplatin-treated A549 cells...
November 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29103102/combination-of-emricasan-with-ponatinib-synergistically-reduces-ischemia-reperfusion-injury-in-rat-brain-through-simultaneous-prevention-of-apoptosis-and-necroptosis
#5
Jing Tian, Shu Guo, Heng Chen, Jing-Jie Peng, Miao-Miao Jia, Nian-Sheng Li, Xiao-Jie Zhang, Jie Yang, Xiu-Ju Luo, Jun Peng
Apoptosis and receptor-interacting protein kinase 1/3(RIPK1/3)-mediated necroptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. Emricasan is an inhibitor of caspases in clinical trials for liver diseases while ponatinib could be a potential inhibitor for RIPK1/3. This study aims to investigate the effect of emricasan and/or ponatinib on cerebral I/R injury and the underlying mechanisms. Firstly, we evaluated the status of apoptosis and necroposis in a rat model of cerebral I/R under different conditions, which showed noticeable apoptosis and necroptosis under condition of 2-h ischemia and 24-h reperfusion; next, the preventive or therapeutic effect of emricasan or ponatinib on cerebral I/R injury was tested...
November 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29101355/particles-of-different-sizes-and-shapes-induce-neutrophil-necroptosis-followed-by-the-release-of-neutrophil-extracellular-trap-like-chromatin
#6
Jyaysi Desai, Orestes Foresto-Neto, Mohsen Honarpisheh, Stefanie Steiger, Daigo Nakazawa, Bastian Popper, Eva Miriam Buhl, Peter Boor, Shrikant R Mulay, Hans-Joachim Anders
The human body is exposed to a wide range of particles of industrial, environmental or internal origin such as asbestos, alum, silica or crystals of urate, calcium phosphate, calcium oxalate, cystine or cholesterol. Phagocytic clearance of such particles involves neutrophils and macrophages. Here we report that neutrophils encountering such particles of diverse sizes and shapes undergo necrotic cell death, a process associated with the formation of neutrophil extracellular trap (NET)-like extracellular DNA...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29098922/overexpression-of-u1-snrna-induces-decrease-of-u1-spliceosome-function-associated-with-alzheimer-s-disease
#7
Zhi Cheng, Yingchun Shang, Shan Gao, Tao Zhang
We recently reported that presenilin-1 (PS1) induced an increase of U1 snRNA expression accompanied with the change of amyloid precursor protein expression, β-amyloid level and cell death. In the present study, our data showed that both overexpression and knockdown of U1 snRNA could cause the loss in the function of U1 snRNA and resulted in PCPA as well as the same downstream phenomena including the expression changes of genes specific to AD, tau hyperphosphorylation on the site of Thr212, the decrease of acetylated α-tubulin, the reduction of cell viability and upregulation of RIPK1, RIPK3 and caspase8...
November 3, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/29089374/autophagy-protein-atg16l1-prevents-necroptosis-in-the-intestinal-epithelium
#8
Yu Matsuzawa-Ishimoto, Yusuke Shono, Luis E Gomez, Vanessa M Hubbard-Lucey, Michael Cammer, Jessica Neil, M Zahidunnabi Dewan, Sophia R Lieberman, Amina Lazrak, Jill M Marinis, Allison Beal, Philip A Harris, John Bertin, Chen Liu, Yi Ding, Marcel R M van den Brink, Ken Cadwell
A variant of the autophagy gene ATG16L1 is associated with Crohn's disease, an inflammatory bowel disease (IBD), and poor survival in allogeneic hematopoietic stem cell transplant recipients. We demonstrate that ATG16L1 in the intestinal epithelium is essential for preventing loss of Paneth cells and exaggerated cell death in animal models of virally triggered IBD and allogeneic hematopoietic stem cell transplantation. Intestinal organoids lacking ATG16L1 reproduced this loss in Paneth cells and displayed TNFα-mediated necroptosis, a form of programmed necrosis...
October 31, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29078411/peli1-functions-as-a-dual-modulator-of-necroptosis-and-apoptosis-by-regulating-ubiquitination-of-ripk1-and-mrna-levels-of-c-flip
#9
Huibing Wang, Huyan Meng, Xingyan Li, Kezhou Zhu, Kangyun Dong, Adnan K Mookhtiar, Huiting Wei, Ying Li, Shao-Cong Sun, Junying Yuan
Apoptosis and necroptosis are two distinct cell death mechanisms that may be activated in cells on stimulation by TNFα. It is still unclear, however, how apoptosis and necroptosis may be differentially regulated. Here we screened for E3 ubiquitin ligases that could mediate necroptosis. We found that deficiency of Pellino 1 (PELI1), an E3 ubiquitin ligase, blocked necroptosis. We show that PELI1 mediates K63 ubiquitination on K115 of RIPK1 in a kinase-dependent manner during necroptosis. Ubiquitination of RIPK1 by PELI1 promotes the formation of necrosome and execution of necroptosis...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29078325/necroptosis-controls-net-generation-and-mediates-complement-activation-endothelial-damage-and-autoimmune-vasculitis
#10
Adrian Schreiber, Anthony Rousselle, Jan Ulrich Becker, Anne von Mässenhausen, Andreas Linkermann, Ralph Kettritz
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes life-threatening autoimmune diseases affecting every organ, including the kidneys, where they cause necrotizing crescentic glomerulonephritis. ANCA activates neutrophils and activated neutrophils damage the endothelium, leading to vascular inflammation and necrosis. Better understanding of neutrophil-mediated AAV disease mechanisms may reveal novel treatment strategies. Here we report that ANCA induces neutrophil extracellular traps (NETs) via receptor-interacting protein kinase (RIPK) 1/3- and mixed-lineage kinase domain-like (MLKL)-dependent necroptosis...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29050220/characterization-of-a-novel-androgen-receptor-ar-coregulator-ripk1-and-related-chemicals-that-suppress-ar-mediated-prostate-cancer-growth-via-peptide-and-chemical-screening
#11
Cheng-Lung Hsu, Jai-Shin Liu, Ting-Wei Lin, Ying-Hsu Chang, Yung-Chia Kuo, An-Chi Lin, Huei-Ju Ting, See-Tong Pang, Li-Yu Lee, Wen-Lung Ma, Chun-Cheng Lin, Wen-Guey Wu
Using bicalutamide-androgen receptor (AR) DNA binding domain-ligand binding domain as bait, we observed enrichment of FxxFY motif-containing peptides. Protein database searches revealed the presence of receptor-interacting protein kinase 1 (RIPK1) harboring one FxxFY motif. RIPK1 interacted directly with AR and suppressed AR transactivation in a dose-dependent manner. Domain mapping experiments showed that the FxxFY motif in RIPK1 is critical for interactions with AR and the death domain of RIPK1 plays a crucial role in its inhibitory effect on transactivation...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29037260/a-novel-protein-derived-from-lamprey-supraneural-body-tissue-with-efficient-cytocidal-actions-against-tumor-cells
#12
Yue Pang, Changzhi Li, Shiyue Wang, Wei Ba, Tao Yu, Guangying Pei, Dan Bi, Hongfang Liang, Xiong Pan, Ting Zhu, Meng Gou, Yinglun Han, Qingwei Li
BACKGROUND: In previous research, we found that cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells, but the protein with cytocidal activity was unidentified. METHODS: A novel lamprey immune protein (LIP) as defense molecule was first purified and identified in jawless vertebrates (cyclostomes) using hydroxyapatite column and Q Sepharose Fast Flow column. After LIP stimulation, morphological changes of tumor cells were analysed and measured whether in vivo or in vitro...
October 16, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29026104/cetsa-quantitatively-verifies-in-vivo-target-engagement-of-novel-ripk1-inhibitors-in-various-biospecimens
#13
Tsuyoshi Ishii, Takuro Okai, Misa Iwatani-Yoshihara, Manabu Mochizuki, Satoko Unno, Masako Kuno, Masato Yoshikawa, Sachio Shibata, Masanori Nakakariya, Takatoshi Yogo, Tomohiro Kawamoto
The proof of target engagement (TE) is a key element for evaluating potential investment in drug development. The cellular thermal shift assay (CETSA) is expected to facilitate direct measurement of intracellular TE at all stages of drug development. However, there have been no reports of applying this technology to comprehensive animal and clinical studies. This report demonstrates that CETSA can not only quantitatively evaluate the drug-TE in mouse peripheral blood, but also confirm TE in animal tissues exemplified by using the receptor interacting protein 1 kinase (RIPK1) lead compound we have developed...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29018243/6e11-a-highly-selective-inhibitor-of-receptor-interacting-protein-kinase-1-protects-cells-against-cold-hypoxia-reoxygenation-injury
#14
C Delehouzé, S Leverrier-Penna, F Le Cann, A Comte, M Jacquard-Fevai, O Delalande, N Desban, B Baratte, I Gallais, F Faurez, M C Bonnet, M Hauteville, P G Goekjian, R Thuillier, F Favreau, P Vandenabeele, T Hauet, M T Dimanche-Boitrel, S Bach
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993228/kinase-independent-role-of-nuclear-ripk1-in-regulating-parthanatos-through-physical-interaction-with-parp1-upon-oxidative-stress
#15
Ki-Hong Jang, Taeik Jang, Eunji Son, Soonjin Choi, Eunhee Kim
Regulated necrosis occurs in various pathophysiological conditions under oxidative stress. Here, we report that receptor-interacting protein kinase 1 (RIPK1), a key player in one type of regulated necrosis (necroptosis), also participates in another type of poly (ADP-ribose) polymerase 1 (PARP1)-dependent regulated necrosis (parthanatos). Various biological signatures of parthanatos were significantly attenuated in Ripk1(-/-) mouse embryonic fibroblasts, including PARylation, nuclear translocation of apoptosis-inducing factor, and PARP1-dependent cell death under H2O2 exposure...
October 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28975372/t-buooh-induces-ferroptosis-in-human-and-murine-cell-lines
#16
Christine Wenz, Dagmar Faust, Berenike Linz, Christian Turmann, Teodora Nikolova, John Bertin, Peter Gough, Peter Wipf, Anna Sophia Schröder, Stefan Krautwald, Cornelia Dietrich
Reactive oxygen species (ROS)-induced apoptosis has been extensively studied. Increasing evidence suggests that ROS, for instance, induced by hydrogen peroxide (H2O2), might also trigger regulated necrotic cell death pathways. Almost nothing is known about the cell death pathways triggered by tertiary-butyl hydroperoxide (t-BuOOH), a widely used inducer of oxidative stress. The lipid peroxidation products induced by t-BuOOH are involved in the pathophysiology of many diseases, such as cancer, cardiovascular diseases, or diabetes...
October 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28973950/ripk1-promotes-inflammation-and-%C3%AE-amyloid-accumulation-in-alzheimer-s-disease
#17
David C Rubinsztein
No abstract text is available yet for this article.
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28970360/heat-shock-protein-70-hsp70-suppresses-rip1-dependent-apoptotic-and-necroptotic-cascades
#18
Sharan R Srinivasan, Laura C Cesa, Xiaokai Li, Olivier Julien, MIn Zhuang, Hao Shao, Jooho Chung, Ivan Maillard, James A Wells, Colin Duckett, Jason E Gestwicki
Heat shock protein 70 (Hsp70) is a molecular chaperone that binds to "client" proteins and protects them from protein degradation. Hsp70 is essential for the survival of many cancer cells, but it is not yet clear which of its clients are involved. Using structurally distinct chemical inhibitors, we found that many of the well-known clients of the related chaperone, Hsp90, are not strikingly responsive to Hsp70 inhibition. Rather, Hsp70 appeared to be important for the stability of the RIP1 (RIPK1) regulators: cIAP1/2 (BIRC1 and BIRC3), XIAP, and cFLIPS/L (CFLAR)...
September 28, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28933271/targeting-cell-necroptosis-and-apoptosis-induced-by-shikonin-via-receptor-interacting-protein-kinases-in-estrogen-receptor-positive-breast-cancer-cell-line-mcf-7
#19
Zahra Shahsavari, Fatemeh Karami-Tehrani, Siamak Salami
Recognition of a new therapeutic agent may activate an alternative programmed cell death for the treatment of breast cancer. Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast cancer cell line, MCF-7. In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions, caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been evaluated in the Shikonin-treated MCF-7 cells...
September 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28920954/p38-mapk-mk2-dependent-phosphorylation-controls-cytotoxic-ripk1-signalling-in-inflammation-and%C3%A2-infection
#20
Manoj B Menon, Julia Gropengießer, Jessica Fischer, Lena Novikova, Anne Deuretzbacher, Juri Lafera, Hanna Schimmeck, Nicole Czymmeck, Natalia Ronkina, Alexey Kotlyarov, Martin Aepfelbacher, Matthias Gaestel, Klaus Ruckdeschel
Receptor-interacting protein kinase-1 (RIPK1), a master regulator of cell fate decisions, was identified as a direct substrate of MAPKAP kinase-2 (MK2) by phosphoproteomic screens using LPS-treated macrophages and stress-stimulated embryonic fibroblasts. p38(MAPK)/MK2 interact with RIPK1 in a cytoplasmic complex and MK2 phosphorylates mouse RIPK1 at Ser321/336 in response to pro-inflammatory stimuli, such as TNF and LPS, and infection with the pathogen Yersinia enterocolitica. MK2 phosphorylation inhibits RIPK1 autophosphorylation, curtails RIPK1 integration into cytoplasmic cytotoxic complexes, and suppresses RIPK1-dependent apoptosis and necroptosis...
October 2017: Nature Cell Biology
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