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Cell Death and Differentiation

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https://www.readbyqxmd.com/read/29339775/anti-apoptotic-a1-is-not-essential-for-lymphoma-development-in-e%C3%A2%C2%B5-myc-mice-but-helps-sustain-transplanted-e%C3%A2%C2%B5-myc-tumour-cells
#1
Mark Mensink, Natasha S Anstee, Mikara Robati, Robyn L Schenk, Marco J Herold, Suzanne Cory, Cassandra J Vandenberg
The transcription factor c-MYC regulates a multiplicity of genes involved in cellular growth, proliferation, metabolism and DNA damage response and its overexpression is a hallmark of many tumours. Since MYC promotes apoptosis under conditions of stress, such as limited availability of nutrients or cytokines, MYC-driven cells are very much dependent on signals that inhibit cell death. Stress signals trigger apoptosis via the pathway regulated by opposing fractions of the BCL-2 protein family and previous genetic studies have shown that the development of B lymphoid tumours in Eµ-Myc mice is critically dependent on expression of pro-survival BCL-2 relatives MCL-1, BCL-W and, to a lesser extent, BCL-XL, but not BCL-2 itself, and that sustained growth of these lymphomas is dependent on MCL-1...
January 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29323266/aif-loss-deregulates-hematopoiesis-and-reveals-different-adaptive-metabolic-responses-in-bone-marrow-cells-and-thymocytes
#2
Lauriane Cabon, Audrey Bertaux, Marie-Noëlle Brunelle-Navas, Ivan Nemazanyy, Laurianne Scourzic, Laure Delavallée, Laura Vela, Mathieu Baritaud, Sandrine Bouchet, Cécile Lopez, Vu Quang Van, Kevin Garbin, Danielle Chateau, Françoise Gilard, Marika Sarfati, Thomas Mercher, Olivier A Bernard, Santos A Susin
Mitochondrial metabolism is a tightly regulated process that plays a central role throughout the lifespan of hematopoietic cells. Herein, we analyze the consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism disorder associated with the cell-specific hematopoietic ablation of apoptosis-inducing factor (AIF). AIF-null (AIF-/Y ) mice developed pancytopenia that was associated with hypocellular bone marrow (BM) and thymus atrophy. Although myeloid cells were relatively spared, the B-cell and erythroid lineages were altered with increased frequencies of precursor B cells, pro-erythroblasts I, and basophilic erythroblasts II...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29323265/redox-dependent-bmi1-activity-drives-in-vivo-adult-cardiac-progenitor-cell-differentiation
#3
Diego Herrero, María Tomé, Susana Cañón, Francisco M Cruz, Rosa María Carmona, Encarna Fuster, Enrique Roche, Antonio Bernad
Accumulation of reactive oxygen species (ROS) is associated with several cardiovascular pathologies and with cell cycle exit by neonanatal cardiomyocytes, a key limiting factor in the regenerative capacity of the adult mammalian heart. The polycomb complex component BMI1 is linked to adult progenitors and is an important partner in DNA repair and redox regulation. We found that high BMI1 expression is associated with an adult Sca1+ cardiac progenitor sub-population with low ROS levels. In homeostasis, BMI1 repressed cell fate genes, including a cardiogenic differentiation program...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29323264/orai3-calcium-channel-and-resistance-to-chemotherapy-in-breast-cancer-cells-the-p53-connection
#4
Jessy Hasna, Frédéric Hague, Lise Rodat-Despoix, Dirk Geerts, Catherine Leroy, David Tulasne, Halima Ouadid-Ahidouch, Philippe Kischel
Orai proteins are highly selective calcium channels playing an important role in calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues, and involved in their proliferation, cell cycle progression and survival. Herein, we sought to address the involvement of Orai3 in resistance to chemotherapeutic drugs. Using high-throughput approaches, we investigated major changes induced by Orai3 overexpression, including downstream signaling mechanisms involved in BC chemotherapy resistance. Resistance was dependent on external calcium presence and thus Orai3 functionality...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29317762/carnitine-palmitoyltransferase-1c-regulates-cancer-cell-senescence-through-mitochondria-associated-metabolic-reprograming
#5
Yongtao Wang, Yixin Chen, Lihuan Guan, Huizheng Zhang, Yaoyao Huang, Caroline H Johnson, Zeming Wu, Frank J Gonzalez, Aiming Yu, Peng Huang, Ying Wang, Shouhui Yang, Pan Chen, Xiaomei Fan, Min Huang, Huichang Bi
Cellular senescence is a fundamental biological process that has profound implications in cancer development and therapeutics, but the underlying mechanisms remain elusive. Here we show that carnitine palmitoyltransferase 1C (CPT1C), an enzyme that catalyzes carnitinylation of fatty acids for transport into mitochondria for β-oxidation, plays a major role in the regulation of cancer cell senescence through mitochondria-associated metabolic reprograming. Metabolomics analysis suggested alterations in mitochondria activity, as revealed by the marked decrease in acylcarnitines in senescent human pancreatic carcinoma PANC-1 cells, indicating low CPT1C activity...
January 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29317761/mk2-puts-an-additional-brake-on-ripk1-cytotoxic-potential
#6
Yves Dondelinger, Tom Delanghe, Mathieu M J Bertrand
No abstract text is available yet for this article.
January 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29311623/basal-p53-expression-is-indispensable-for-mesenchymal-stem-cell-integrity
#7
Siddaraju V Boregowda, Veena Krishnappa, Jacqueline Strivelli, Christopher L Haga, Cori N Booker, Donald G Phinney
Marrow-resident mesenchymal stem cells (MSCs) serve as a functional component of the perivascular niche that regulates hematopoiesis. They also represent the main source of bone formed in adult bone marrow, and their bifurcation to osteoblast and adipocyte lineages plays a key role in skeletal homeostasis and aging. Although the tumor suppressor p53 also functions in bone organogenesis, homeostasis, and neoplasia, its role in MSCs remains poorly described. Herein, we examined the normal physiological role of p53 in primary MSCs cultured under physiologic oxygen levels...
January 8, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29311622/dual-roles-of-trf1-in-tethering-telomeres-to-the-nuclear-envelope-and-protecting-them-from-fusion-during-meiosis
#8
Lina Wang, Zhaowei Tu, Chao Liu, Hongbin Liu, Philipp Kaldis, Zijiang Chen, Wei Li
Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the failure of recruiting meiosis specific telomere associated proteins...
January 8, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29305587/consensus-molecular-subtypes-of-colorectal-cancer-are-recapitulated-in-in-vitro-and-in-vivo-models
#9
Janneke F Linnekamp, Sander R van Hooff, Pramudita R Prasetyanti, Raju Kandimalla, Joyce Y Buikhuisen, Evelyn Fessler, Prashanthi Ramesh, Kelly A S T Lee, Grehor G W Bochove, Johan H de Jong, Kate Cameron, Ronald van Leersum, Hans M Rodermond, Marek Franitza, Peter Nürnberg, Laura R Mangiapane, Xin Wang, Hans Clevers, Louis Vermeulen, Giorgio Stassi, Jan Paul Medema
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed...
January 5, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29305586/efficient-generation-of-functional-haploid-spermatids-from-human-germline-stem-cells-by-three-dimensional-induced-system
#10
Min Sun, Qingqing Yuan, Minghui Niu, Hong Wang, Liping Wen, Chencheng Yao, Jingmei Hou, Zheng Chen, Hongyong Fu, Fan Zhou, Chong Li, Shaorong Gao, Wei-Qiang Gao, Zheng Li, Zuping He
Generation of functional spermatids from human spermatogonial stem cells (SSCs) in vitro is of utmost importance for uncovering mechanisms underlying human germ cell development and treating infertility. Here we report a three-dimensional-induced (3D-I) system by which human SSCs were efficiently differentiated into functional haploid spermatids. Human SSCs were isolated and identified phenotypically. Meiotic chromatin spreads and DNA content assays revealed that spermatocytes and haploid cells were effectively generated from human SSCs by 3D-I system...
January 5, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29305585/sumoylation-of-notch1-represses-its-target-gene-expression-during-cell-stress
#11
Christian J M Antila, Vilma Rraklli, Henri A Blomster, Käthe M Dahlström, Tiina A Salminen, Johan Holmberg, Lea Sistonen, Cecilia Sahlgren
The Notch signaling pathway is a key regulator of stem cells during development, and its deregulated activity is linked to developmental defects and cancer. Transcriptional activation of Notch target genes requires cleavage of the Notch receptor in response to ligand binding, production of the Notch intracellular domain (NICD1), NICD1 migration into the nucleus, and assembly of a transcriptional complex. Post-translational modifications of Notch regulate its trafficking, turnover, and transcriptional activity...
January 5, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29302057/diabetes-induces-the-activation-of-pro-ageing-mir-34a-in-the-heart-but-has-differential-effects-on-cardiomyocytes-and-cardiac-progenitor-cells
#12
Ingrid Fomison-Nurse, Eugene Eng Leng Saw, Sophie Gandhi, Pujika Emani Munasinghe, Isabelle Van Hout, Michael J A Williams, Ivor Galvin, Richard Bunton, Philip Davis, Vicky Cameron, Rajesh Katare
Increased apoptosis and premature cellular ageing of the diabetic heart underpin the development of diabetic heart disease. The molecular mechanisms underlying these pathologies are still unclear. Here we determined the role of pro-senescence microRNA (miR)-34a in accelerating the ageing of the diabetic heart. RT-PCR analysis showed a significant increase in the level of circulating miR-34a from early stages in asymptomatic type-2 diabetic individuals compared to non-diabetic controls. We also observed significant upregulation of miR-34a in the type-2 human diabetic heart suggesting circulating miR-34a may be cardiac in origin...
January 4, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29244050/cd52-inhibits-toll-like-receptor-activation-of-nf-%C3%AE%C2%BAb-and-triggers-apoptosis-to-suppress-inflammation
#13
Maryam Rashidi, Esther Bandala-Sanchez, Kate E Lawlor, Yuxia Zhang, Alana M Neale, Swarna L Vijayaraj, Robert O'Donoghue, John M Wentworth, Timothy E Adams, James E Vince, Leonard C Harrison
Soluble CD52 is a small glycoprotein that suppresses T-cell activation, but its effect on innate immune cell function is unknown. Here we demonstrate that soluble CD52 inhibits Toll-like receptor and tumor necrosis factor receptor signaling to limit activation of NF-κB and thereby suppress the production of inflammatory cytokines by macrophages, monocytes and dendritic cells. At higher concentrations, soluble CD52 depletes the short-lived pro-survival protein MCL-1, contributing to activation of the BH3-only proteins BAX and BAK to cause intrinsic apoptotic cell death...
December 15, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29238073/stage-dependent-therapeutic-efficacy-in-pi3k-mtor-driven-squamous-cell-carcinoma-of-the-skin
#14
Charbel Darido, Smitha R Georgy, Carleen Cullinane, Darren D Partridge, Rachael Walker, Seema Srivastava, Suraya Roslan, Marina R Carpinelli, Sebastian Dworkin, Richard B Pearson, Stephen M Jane
Cutaneous squamous cell carcinoma (SCC) is a recurrent cancer that is prevalent in predisposed subjects such as immunosuppressed patients and patients being treated for other malignancies. Model systems to trial therapies at different stages of SCC development are lacking, therefore precluding efficient therapeutic interventions. Here, we have disrupted the expression of the tumor suppressor GRHL3 to induce loss of PTEN and activation of the PI3K/mTOR signaling pathway in mice and human skin, promoting aggressive SCC development...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29238072/tissue-transglutaminase-in-the-pathogenesis-of-heart-failure
#15
Arti V Shinde, Nikolaos G Frangogiannis
No abstract text is available yet for this article.
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29238071/app-upregulation-contributes-to-retinal-ganglion-cell-degeneration-via-jnk3
#16
Chao Liu, Cheng-Wu Zhang, Yi Zhou, Wan Qing Wong, Liying Corinne Lee, Wei Yi Ong, Sung Ok Yoon, Wanjin Hong, Xin-Yuan Fu, Tuck Wah Soong, Edward H Koo, Lawrence W Stanton, Kah-Leong Lim, Zhi-Cheng Xiao, Gavin S Dawe
Axonal injury is a common feature of central nervous system insults. Upregulation of amyloid precursor protein (APP) is observed following central nervous system neurotrauma and is regarded as a marker of central nervous system axonal injury. However, the underlying mechanism by which APP mediates neuronal death remains to be elucidated. Here, we used mouse optic nerve axotomy (ONA) to model central nervous system axonal injury replicating aspects of retinal ganglion cell (RGC) death in optic neuropathies. APP and APP intracellular domain (AICD) were upregulated in retina after ONA and APP knockout reduced Tuj1+ RGC loss...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29238070/the-interplay-between-mutant-p53-and-the-mevalonate-pathway
#17
REVIEW
Alejandro Parrales, Elizabeth Thoenen, Tomoo Iwakuma
Missense mutations in the TP53 gene lead to accumulation of dysfunctional TP53 proteins in tumors, showing oncogenic gain-of-function (GOF) activities. Stabilization of mutant TP53 (mutp53) is required for the GOF; however, the mechanisms by which mutp53 promotes cancer progression and how mutp53 stability is regulated are not completely understood. Recent work from our laboratory has identified statins, inhibitors of the mevalonate pathway, as degraders of conformational mutp53. Specific reduction of mevalonate-5-phosphate (MVP), a metabolic intermediate in the mevalonate pathway, by statins or mevalonate kinase (MVK) knockdown triggers CHIP ubiquitin ligase-mediated degradation of conformational mutp53 by inhibiting interaction between mutp53 and DNAJA1, a Hsp40 family member...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29238069/kynurenic-acid-an-ido-metabolite-controls-tsg-6-mediated-immunosuppression-of-human-mesenchymal-stem-cells
#18
Guan Wang, Kai Cao, Keli Liu, Yueqing Xue, Arthur I Roberts, Fengying Li, Yanyan Han, Arnold B Rabson, Ying Wang, Yufang Shi
Mesenchymal stem cells (MSCs) have been demonstrated to be anti-inflammatory against various immune disorders through several factors, including indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene 6 (TSG-6). However, little is known about the necessity for both of these key immunosuppressive factors. Here we employed the mouse lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and found that IDO is necessary to achieve the effect of human umbilical cord-derived MSC (hUC-MSC)-based treatment on ALI...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29234155/analysis-of-neuronal-phosphoproteome-reveals-pink1-regulation-of-bad-function-and-cell-death
#19
Huida Wan, Bin Tang, Xun Liao, Qiufang Zeng, Zhuohua Zhang, Lujian Liao
PINK1 mutations that disrupt its kinase activity cause autosomal recessive early onset Parkinson's disease (PD). Although research in recent years has elucidated a PINK1-Parkin pathway of mitophagy activation that requires PINK1 kinase activity, mitophagy-independent functions of PINK1 and their possible roles in PD pathogenesis have been proposed. Using an unbiased quantitative mass spectrometry approach to analyze the phosphoproteome in primary neurons from wild type and Pink1 knockout mice after mitochondrial depolarization, we uncovered PINK1-regulated phosphorylation sites, which involve coordinated activation of multiple signaling pathways that control cellular response to stress...
December 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29230002/deficiency-in-interferon-type-1-receptor-improves-definitive-erythropoiesis-in-klf1-null-mice
#20
Maria Francesca Manchinu, Carla Brancia, Cristian Antonio Caria, Ester Musu, Susanna Porcu, Michela Simbula, Isadora Asunis, Lucia Perseu, Maria Serafina Ristaldi
A key regulatory gene in definitive erythropoiesis is the transcription factor Krüppel-like factor 1 (Klf1). Klf1 null mice die in utero by day 15.5 (E15.5) due to impaired definitive erythropoiesis and severe anemia. Definitive erythropoiesis takes place in erythroblastic islands in mammals. Erythroblastic islands are formed by a central macrophage (Central Macrophage of Erythroblastic Island, CMEI) surrounded by maturating erythroblasts. Interferon-β (IFN-β) is activated in the fetal liver's CMEI of Klf1 null mice...
December 11, 2017: Cell Death and Differentiation
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