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Cell Death and Differentiation

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https://www.readbyqxmd.com/read/28085151/the-bcl-2-pro-survival-protein-a1-is-dispensable-for-t-cell-homeostasis-on-viral-infection
#1
Selma Tuzlak, Robyn L Schenk, Ajithkumar Vasanthakumar, Simon P Preston, Manuel D Haschka, Dimitra Zotos, Axel Kallies, Andreas Strasser, Andreas Villunger, Marco J Herold
The physiological role of the pro-survival BCL-2 family member A1 has been debated for a long time. Strong mRNA induction in T cells on T cell receptor (TCR)-engagement suggested a major role of A1 in the survival of activated T cells. However, the investigation of the physiological roles of A1 was complicated by the quadruplication of the A1 gene locus in mice, making A1 gene targeting very difficult. Here, we used the recently generated A1(-/-) mouse model to examine the role of A1 in T cell immunity. We confirmed rapid and strong induction of A1 protein in response to TCR/CD3 stimulation in CD4(+) as well as CD8(+) T cells...
January 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28085150/characterisation-of-mice-lacking-all-functional-isoforms-of-the-pro-survival-bcl-2-family-member-a1-reveals-minor-defects-in-the-haematopoietic-compartment
#2
Robyn L Schenk, Selma Tuzlak, Emma M Carrington, Yifan Zhan, Susanne Heinzel, Charis E Teh, Daniel H Gray, Lin Tai, Andrew M Lew, Andreas Villunger, Andreas Strasser, Marco J Herold
The pro-survival proteins of the BCL-2 family regulate the survival of all cells, and genetic deletion models for these proteins have revealed which specific BCL-2 family member(s) is/are critical for the survival of particular cell types. A1 is a pro-survival BCL-2-like protein that is expressed predominantly in haematopoietic cells, and here we describe the characterisation of a novel mouse strain that lacks all three functional isoforms of A1 (A1-a, A1-b and A1-d). Surprisingly, complete loss of A1 caused only minor defects, with significant, although relatively small, decreases in γδTCR T cells, antigen-experienced conventional as well as regulatory CD4 T cells and conventional dendritic cells (cDCs)...
January 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28085149/aposod1-lacking-dismutase-activity-neuroprotects-motor-neurons-exposed-to-beta-methylamino-l-alanine-through-the-ca-2-akt-erk1-2-prosurvival-pathway
#3
Tiziana Petrozziello, Agnese Secondo, Valentina Tedeschi, Alba Esposito, MariaJosè Sisalli, Antonella Scorziello, Gianfranco Di Renzo, Lucio Annunziato
Amyotrophic lateral sclerosis (ALS) is a severe human adult-onset neurodegenerative disease affecting lower and upper motor neurons. In >20% of cases, the familial form of ALS is caused by mutations in the gene encoding Cu,Zn-superoxide dismutase (SOD1). Interestingly, administration of wild-type SOD1 to SOD1(G93A) transgenic rats ameliorates motor symptoms through an unknown mechanism. Here we investigated whether the neuroprotective effects of SOD1 are due to the Ca(2+)-dependent activation of such prosurvival signaling pathway and not to its catalytic activity...
January 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060382/epigenetic-control-of-mitochondrial-cell-death-through-pacs1-mediated-regulation-of-bax-bak-oligomerization
#4
Daniella Brasacchio, Amber E Alsop, Tahereh Noori, Mariam Lufti, Sweta Iyer, Kaylene J Simpson, Phillip I Bird, Ruth M Kluck, Ricky W Johnstone, Joseph A Trapani
PCAF and ADA3 associate within the same macromolecular complexes to control the transcription of many genes, including some that regulate apoptosis. Here we show that PCAF and ADA3 regulate the expression of PACS1, whose protein product is a key component of the machinery that sorts proteins among the trans-Golgi network and the endosomal compartment. We describe a novel role for PACS1 as a regulator of the intrinsic pathway of apoptosis and mitochondrial outer membrane permeabilization. Cells with decreased PACS1 expression were refractory to cell death mediated by a variety of stimuli that operate through the mitochondrial pathway, including human granzyme B, staurosporine, ultraviolet radiation and etoposide, but remained sensitive to TRAIL receptor ligation...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060381/kctd2-an-adaptor-of-cullin3-e3-ubiquitin-ligase-suppresses-gliomagenesis-by-destabilizing-c-myc
#5
Eun-Jung Kim, Sung-Hak Kim, Xiong Jin, Xun Jin, Hyunggee Kim
Cullin3 E3 ubiquitin ligase ubiquitinates a wide range of substrates through substrate-specific adaptors Bric-a-brac, Tramtrack, and Broad complex (BTB) domain proteins. These E3 ubiquitin ligase complexes are involved in diverse cellular functions. Our recent study demonstrated that decreased Cullin3 expression induces glioma initiation and correlates with poor prognosis of patients with malignant glioma. However, the substrate recognition mechanism associated with tumorigenesis is not completely understood...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060380/neutralizing-gp130-interferes-with-endothelial-mediated-effects-on-glioblastoma-stem-like-cells
#6
Kathryn A Jacobs, Elizabeth Harford-Wright, Julie Gavard
No abstract text is available yet for this article.
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060379/one-carbon-many-roads
#7
Eyal Gottlieb, Karen H Vousden
No abstract text is available yet for this article.
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060378/cd73-regulates-anti-inflammatory-signaling-between-apoptotic-cells-and-endotoxin-conditioned-tissue-macrophages
#8
Patrick S Murphy, Jing Wang, Samir P Bhagwat, Joshua C Munger, William J Janssen, Terry W Wright, Michael R Elliott
The phagocytosis of apoptotic cells (efferocytosis) shifts macrophages to an anti-inflammatory state through a set of still poorly understood soluble and cell-bound signals. Apoptosis is a common feature of inflamed tissues, and efferocytosis by tissue macrophages is thought to promote the resolution of inflammation. However, it is not clear how the exposure of tissue macrophages to inflammatory cues (e.g., PAMPs, DAMPs) in the early stages of inflammation affects immune outcomes of macrophage-apoptotic cell interactions occurring at later stages of inflammation...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060377/microrna-29c-5p-suppresses-gallbladder-carcinoma-progression-by-directly-targeting-cpeb4-and-inhibiting-the-mapk-pathway
#9
Yi-Jun Shu, Run-Fa Bao, Lin Jiang, Zheng Wang, Xu-An Wang, Fei Zhang, Han-Bin Liang, Huai-Feng Li, Yuan-Yuan Ye, Shan-Shan Xiang, Hao Weng, Xiang-Song Wu, Mao-Lan Li, Yun-Ping Hu, Wei Lu, Yi-Jian Zhang, Jian Zhu, Ping Dong, Ying-Bin Liu
Gallbladder cancer (GBC) is a leading cause of cancer-related deaths worldwide, and its prognosis remains poor, with a 5-year survival rate of ~5%. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of the metastasis-associated miRNA miR-29c-5p in GBC.We validated that expression of miR-29c-5p was significantly downregulated in GBC and was closely associated with lymph node metastasis, overall survival and disease-free survival in 40 GBC patients who were followed clinically...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060376/induction-of-necroptotic-cell-death-by-viral-activation-of-the-rig-i-or-sting-pathway
#10
Suruchi N Schock, Neha V Chandra, Yuefang Sun, Takashi Irie, Yoshinori Kitagawa, Bin Gotoh, Laurent Coscoy, Astar Winoto
Necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase RIP1 and its family member RIP3. Necroptosis occurs when RIP1 is deubiquitinated to form a complex with RIP3 in cells deficient in the death receptor adapter molecule FADD or caspase-8. Necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. To see how general the interplay between viruses and necroptosis is, we surveyed seven different viruses...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060375/how-ice-lights-the-pyroptosis-fire
#11
Xing Liu, Judy Lieberman
No abstract text is available yet for this article.
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28009354/rsk-mediated-nuclear-accumulation-of-the-cold-shock-y-box-protein-1-controls-proliferation-of-t-cells-and-t-all-blasts
#12
Steffi Gieseler-Halbach, Stefan Meltendorf, Mandy Pierau, Soenke Weinert, Florian H Heidel, Thomas Fischer, Juliane Handschuh, Ruediger C Braun-Dullaeus, Martin Schrappe, Jonathan A Lindquist, Peter R Mertens, Ulrich Thomas, Monika C Brunner-Weinzierl
Deregulated proliferation is key to tumor progression. Although unrestricted proliferation of solid tumor cells correlates with the cold-shock protein Y-box (YB)-binding protein-1 accumulation in the nuclei, little is known about its expression and function in hematopoietic malignancies, such as T-cell acute lymphoblastic leukemia (T-ALL). Here we show that YB-1 protein is highly enriched in the nuclei of activated T cells and malignant human T-ALL cell lines but not in resting T cells. YB-1 S(102) mutations that either mimic (S102D) or prevent phosphorylation (S102N) led to accumulation of YB-1 in the nucleus of T cells or strictly excluded it, respectively...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28009353/pellino-1-promotes-lung-carcinogenesis-via-the-stabilization-of-slug-and-snail-through-k63-mediated-polyubiquitination
#13
Yoon Kyung Jeon, Chung Kwon Kim, Kyung Rim Hwang, Hye-Young Park, Jaemoon Koh, Doo Hyun Chung, Chang-Woo Lee, Geun-Hyoung Ha
Pellino-1 is an E3 ubiquitin ligase acting as a critical mediator for a variety of immune receptor signaling pathways, including Toll-like receptors, interleukin-1 receptor and T-cell receptors. We recently showed that the Pellino-1-transgenic (Tg) mice developed multiple tumors with different subtypes in hematolymphoid and solid organs. However, the molecular mechanism underlying the oncogenic role of Pellino-1 in solid tumors remains unknown. Pellino-1-Tg mice developed adenocarcinoma in the lungs, and Pellino-1 expression was higher in human lung adenocarcinoma cell lines compared with non-neoplastic bronchial epithelial cell lines...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28009352/a-negative-feedback-loop-of-icer-and-nf-%C3%AE%C2%BAb-regulates-tlr-signaling-in-innate-immune-responses
#14
Sihan Lv, Jian Li, Xinchen Qiu, Weida Li, Chao Zhang, Zhen-Ning Zhang, Bing Luan
The NF-κB pathway has important roles in innate immune responses and its regulation is critical to maintain immune homeostasis. Here, we report a newly discovered feedback mechanism for the regulation of this pathway by TLR ligands in macrophages. Lipopolysaccharide (LPS) induced the expression of ICER via p38-mediated activation of CREB in macrophages. ICER, in turn, inhibited the transcriptional activity of NF-κB by direct interaction with the p65 subunit of NF-κB. Deficiency in ICER elevated binding of NF-κB to promoters of pro-inflammatory genes and their subsequent gene expression...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28009351/s-2hg-is-an-immunometabolite-that-shapes-the-t-cell-response
#15
Rob A Cairns, Tak W Mak
No abstract text is available yet for this article.
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28009350/hic1-and-mir-23-27-24-clusters-form-a-double-negative-feedback-loop-in-breast-cancer
#16
Yanbo Wang, Hongwei Liang, Geyu Zhou, Xiuting Hu, Zhengya Liu, Fangfang Jin, Mengchao Yu, Jianfeng Sang, Yong Zhou, Zheng Fu, Chen-Yu Zhang, Weijie Zhang, Ke Zen, Xi Chen
MicroRNAs (miRNAs) have emerged as a major regulator of the initiation and progression of human cancers, including breast cancer. However, the cooperative effects and transcriptional regulation of multiple miRNAs, especially miRNAs that are present in clusters, remain largely undiscovered. Here we showed that all members of the miR-23~27~24 clusters are upregulated and function as oncogenes in breast cancer and simultaneously target HIC1. Furthermore, we found that HIC1 functions as a transcriptional repressor to negatively control the expression of miR-23~27~24 clusters and forms a double-negative (overall positive) feedback loop...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27935584/ketogenesis-contributes-to-intestinal-cell-differentiation
#17
Qingding Wang, Yuning Zhou, Piotr Rychahou, Teresa W-M Fan, Andrew N Lane, Heidi L Weiss, B Mark Evers
The intestinal epithelium undergoes a continual process of proliferation, differentiation and apoptosis. Previously, we have shown that the PI3K/Akt/mTOR pathway has a critical role in intestinal homeostasis. However, the downstream targets mediating the effects of mTOR in intestinal cells are not known. Here, we show that the ketone body β-hydroxybutyrate (βHB), an endogenous inhibitor of histone deacetylases (HDACs) induces intestinal cell differentiation as noted by the increased expression of differentiation markers (Mucin2 (MUC2), lysozyme, IAP, sucrase-isomaltase, KRT20, villin, Caudal-related homeobox transcription factor 2 (CDX2) and p21(Waf1))...
December 9, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27935582/global-ischemia-induces-lysosomal-mediated-degradation-of-mtor-and-activation-of-autophagy-in-hippocampal-neurons-destined-to-die
#18
Jee-Yeon Hwang, Michael Gertner, Fabrizio Pontarelli, Brenda Court-Vazquez, Michael Vander Laan Bennett, Dimitry Ofengeim, Ruth Suzanne Zukin
The mammalian target of rapamycin (mTOR) is a key regulator of cell growth, autophagy, translation, and survival. Dysregulation of mTOR signaling is associated with cancer, diabetes, and autism. However, a role for mTOR signaling in neuronal death is not well delineated. Here we show that global ischemia triggers a transient increase in mTOR phosphorylation at S2448, whereas decreasing p-mTOR and functional activity in selectively vulnerable hippocampal CA1 neurons. The decrease in mTOR coincides with an increase in biochemical markers of autophagy, pS317-ULK-1, pS14-Beclin-1, and LC3-II, a decrease in the cargo adaptor p62, and an increase in autophagic flux, a functional readout of autophagy...
December 9, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#19
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27911442/palmitoylation-of-caspase-6-by-hip14-regulates-its-activation
#20
Niels H Skotte, Shaun S Sanders, Roshni R Singaraja, Dagmar E Ehrnhoefer, Kuljeet Vaid, Xiaofan Qiu, Srinivasaragavan Kannan, Chandra Verma, Michael R Hayden
Caspase-6 (CASP6) has an important role in axonal degeneration during neuronal apoptosis and in the neurodegenerative diseases Alzheimer and Huntington disease. Decreasing CASP6 activity may help to restore neuronal function in these and other diseases such as stroke and ischemia, where increased CASP6 activity has been implicated. The key to finding approaches to decrease CASP6 activity is a deeper understanding of the mechanisms regulating CASP6 activation. We show that CASP6 is posttranslationally palmitoylated by the palmitoyl acyltransferase HIP14 and that the palmitoylation of CASP6 inhibits its activation...
December 2, 2016: Cell Death and Differentiation
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