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Cellular Reprogramming

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https://www.readbyqxmd.com/read/29786657/eukaryotic-translation-initiation-factor-4a-down-regulation-mediates-interleukin-24-induced-apoptosis-through-inhibition-of-translation
#1
Xuelin Zhong, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Aktas, Moira Sauane
Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs)...
May 22, 2018: Cancers
https://www.readbyqxmd.com/read/29784665/srebf1-activity-is-regulated-by-an-ar-mtor-nuclear-axis-in-prostate-cancer
#2
Etienne Audet-Walsh, Mathieu Vernier, Tracey Yee, Chloe E Laflamme, Susan Li, Yonghong Chen, Vincent Giguere
Reprogramming of cellular metabolism is an important feature of prostate cancer (PCa), including altered lipid metabolism. Recently, it was observed that the nuclear fraction of mTOR is essential for the androgen-mediated metabolic reprogramming of PCa cells. Herein, it is demonstrated that the androgen receptor (AR) and mTOR bind to regulatory regions of sterol regulatory element binding transcription factor 1 (SREBF1) to control its expression, while dual activation of these signaling pathways also promotes SREBF1 cleavage and its translocation to the nucleus...
May 21, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29782489/systematic-identification-of-factors-mediating-accelerated-mrna-degradation-in-response-to-changes-in-environmental-nitrogen
#3
Darach Miller, Nathan Brandt, David Gresham
Cellular responses to changing environments frequently involve rapid reprogramming of the transcriptome. Regulated changes in mRNA degradation rates can accelerate reprogramming by clearing or stabilizing extant transcripts. Here, we measured mRNA stability using 4-thiouracil labeling in the budding yeast Saccharomyces cerevisiae during a nitrogen upshift and found that 78 mRNAs are subject to destabilization. These transcripts include Nitrogen Catabolite Repression (NCR) and carbon metabolism mRNAs, suggesting that mRNA destabilization is a mechanism for targeted reprogramming of the transcriptome...
May 21, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29777905/coupling-of-the-polyamine-and-iron-metabolism-pathways-in-the-regulation-of-proliferation-mechanistic-links-to-alterations-in-key-polyamine-biosynthetic-and-catabolic-enzymes
#4
Darius J R Lane, Dong-Hun Bae, Aritee R Siafakas, Yohan Suryo Rahmanto, Lina Al-Akra, Patric J Jansson, Robert A Casero, Des R Richardson
Many biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777051/cd36-initiates-the-secretory-phenotype-during-the-establishment-of-cellular-senescence
#5
Mengyang Chong, Tao Yin, Rui Chen, Handan Xiang, Lifeng Yuan, Yi Ding, Christopher C Pan, Zhen Tang, Peter B Alexander, Yinjun Jia, Qi-Jing Li, Xiao-Fan Wang
Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor CD36 is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli...
May 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29772845/doxycycline-impairs-mitochondrial-function-and-protects-human-glioma-cells-from-hypoxia-induced-cell-death-implications-of-using-tet-inducible-systems
#6
Anna-Luisa Luger, Benedikt Sauer, Nadja I Lorenz, Anna L Engel, Yannick Braun, Martin Voss, Patrick N Harter, Joachim P Steinbach, Michael W Ronellenfitsch
Inducible gene expression is an important tool in molecular biology research to study protein function. Most frequently, the antibiotic doxycycline is used for regulation of so-called tetracycline (Tet)-inducible systems. In contrast to stable gene overexpression, these systems allow investigation of acute and reversible effects of cellular protein induction. Recent reports have already called for caution when using Tet-inducible systems as the employed antibiotics can disturb mitochondrial function and alter cellular metabolism by interfering with mitochondrial translation...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#7
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29768195/reprogramming-of-chromatin-accessibility-in-somatic-cell-nuclear-transfer-is-dna-replication-independent
#8
Mohamed Nadhir Djekidel, Azusa Inoue, Shogo Matoba, Tsukasa Suzuki, Chunxia Zhang, Falong Lu, Lan Jiang, Yi Zhang
Mammalian oocytes have the ability to reset the transcriptional program of differentiated somatic cells into that of totipotent embryos through somatic cell nuclear transfer (SCNT). However, the mechanisms underlying SCNT-mediated reprogramming are largely unknown. To understand the mechanisms governing chromatin reprogramming during SCNT, we profiled DNase I hypersensitive sites (DHSs) in donor cumulus cells and one-cell stage SCNT embryos. To our surprise, the chromatin accessibility landscape of the donor cells is drastically changed to recapitulate that of the in vitro fertilization (IVF)-derived zygotes within 12 hr...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29764852/combined-hdac-and-bromodomain-protein-inhibition-reprograms-tumor-cell-metabolism-and-elicits-synthetic-lethality-in-glioblastoma
#9
Yiru Zhang, Chiaki Tsuge Ishida, Wataru Ishida, Sheng-Fu L Lo, Junfei Zhao, Chang Shu, Elena Bianchetti, Giulio Kleiner, Maria Sanchez-Quintero, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D Siegelin
PURPOSE: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. EXPERIMENTAL DESIGN: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. RESULTS: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29762526/hypoxia-metabolism-and-immune-cell-function
#10
REVIEW
Ewelina Krzywinska, Christian Stockmann
Hypoxia is a hallmark of inflamed, infected or damaged tissue, and the adaptation to inadequate tissue oxygenation is regulated by hypoxia-inducible factors (HIFs). HIFs are key mediators of the cellular response to hypoxia, but they are also associated with pathological stress such as inflammation, bacteriological infection or cancer. In addition, HIFs are central regulators of many innate and adaptive immunological functions, including migration, antigen presentation, production of cytokines and antimicrobial peptides, phagocytosis as well as cellular metabolic reprogramming...
May 15, 2018: Biomedicines
https://www.readbyqxmd.com/read/29759594/liquid-chromatography-mass-spectrometry-based-metabolomics-and-lipidomics-reveal-toxicological-mechanisms-of-bisphenol-f-in-breast-cancer-xenografts
#11
Chao Zhao, Peisi Xie, Hailin Wang, Zongwei Cai
Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts...
May 5, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29758377/global-insights-of-protein-responses-to-cold-stress-in-plants-signaling-defence-and-degradation
#12
Seyyedeh-Sanam Kazemi-Shahandashti, Reza Maali-Amiri
Cold stress (CS) as one of the unfavorable abiotic tensions proceeds different aspects of plant responses. These responses are generated through CS effects on crucial processes such as photosynthesis, energy metabolism, ROS homeostasis, membrane fluidity and cell wall architecture. As a tolerance response, plants apply proteins in various strategies such as transferring the message of cold entrance named as signaling, producing defensive and protective molecules against the stress and degrading some unfavorable or unnecessary proteins to produce other required ones...
May 4, 2018: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29756093/lineage-plasticity-in-cancer-progression-and-treatment
#13
Clémentine Le Magnen, Michael M Shen, Cory Abate-Shen
Historically, it has been widely presumed that differentiated cells are determined during development and become irreversibly committed to their designated fates. In certain circumstances, however, differentiated cells can display plasticity by changing their identity, either by dedifferentiation to a progenitor-like state or by transdifferentiation to an alternative differentiated cell type. Such cellular plasticity can be triggered by physiological or oncogenic stress, or it can be experimentally induced through cellular reprogramming...
March 2018: Annual Review of Cancer Biology
https://www.readbyqxmd.com/read/29755986/implications-of-cellular-aging-in-cardiac-reprogramming
#14
Fabiana Passaro, Gianluca Testa
Aging is characterized by a chronic functional decline of organ systems which leads to tissue dysfunction over time, representing a risk factor for diseases development, including cardiovascular. The aging process occurring in the cardiovascular system involves heart and vessels at molecular and cellular level, with subsequent structural modifications and functional impairment. Several modifications involved in the aging process can be ascribed to cellular senescence, a biological response that limits the proliferation of damaged cells...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29749399/autocrine-tnf-signaling-favors-malignant-cells-in-myelofibrosis-in-a-tnfr2-dependent-fashion
#15
William L Heaton, Anna V Senina, Anthony D Pomicter, Mohamed E Salama, Phillip M Clair, Dongqing Yan, Russell N Bell, Jeremy M Gililland, Josef T Prchal, Thomas O'Hare, Michael W Deininger
Tumor necrosis factor alpha (TNF) is increased in myelofibrosis (MF) and promotes survival of malignant over normal cells. The mechanisms altering TNF responsiveness in MF cells are unknown. We show that the proportion of marrow (BM) cells expressing TNF is increased in MF compared to controls, with the largest differential in primitive cells. Blockade of TNF receptor 2 (TNFR2), but not TNFR1, selectively inhibited colony formation by MF CD34+ and mouse JAK2V617F progenitor cells. Microarray of mouse MPN revealed reduced expression of X-linked inhibitor of apoptosis (Xiap) and mitogen-activated protein kinase 8 (Mapk8) in JAK2V617F relative to JAK2WT cells, which were normalized by TNFR2 but not TNFR1 blockade...
April 18, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749372/the-thioredoxin-1-system-is-essential-for-fueling-dna-synthesis-during-t-cell-metabolic-reprogramming-and-proliferation
#16
Jonathan Muri, Sebastian Heer, Mai Matsushita, Lea Pohlmeier, Luigi Tortola, Tobias Fuhrer, Marcus Conrad, Nicola Zamboni, Jan Kisielow, Manfred Kopf
The thioredoxin-1 (Trx1) system is an important contributor to cellular redox balance and is a sensor of energy and glucose metabolism. Here we show critical c-Myc-dependent activation of the Trx1 system during thymocyte and peripheral T-cell proliferation, but repression during T-cell quiescence. Deletion of thioredoxin reductase-1 (Txnrd1) prevents expansion the CD4- CD8- thymocyte population, whereas Txnrd1 deletion in CD4+ CD8+ thymocytes does not affect further maturation and peripheral homeostasis of αβT cells...
May 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29748591/mir-3662-suppresses-hepatocellular-carcinoma-growth-through-inhibition-of-hif-1%C3%AE-mediated-warburg-effect
#17
Zhiqiang Chen, Xueliang Zuo, Yao Zhang, Guoyong Han, Long Zhang, Jindao Wu, Xuehao Wang
Glucose metabolic reprogramming from oxidative to aerobic glycolysis, referred as the Warburg effect, is a hallmark of tumor cells. Accumulating evidence suggests that a subset of microRNAs play pivotal roles in modulating such reprogramming of glucose metabolism in cancer cells. miR-3662 has been implicated previously in both pro-tumorigenic and anti-tumorigenic effects in several types of cancer. The expression level of miR-3662 is downregulated in acute myeloid leukemia, whereas increased miR-3662 expression is observed in lung adenocarcinoma...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748232/an-allostatic-mechanism-for-m2-pyruvate-kinase-as-an-amino-acid-sensor
#18
Meng Yuan, Iain W McNae, Yiyuan Chen, Elizabeth A Blackburn, Martin A Wear, Paul A M Michels, Linda A Fothergill-Gilmore, Ted Hupp, Malcolm D Walkinshaw
We have tested the effect of all 20 proteinogenic amino acids on the activity of the M2 isoenzyme of pyruvate kinase (M2PYK) and show that within physiologically relevant concentrations, phenylalanine, alanine, tryptophan, methionine, valine, and proline act as inhibitors while histidine and serine act as activators. Size exclusion chromatography has been used to show that all amino acids, whether activators or inhibitors, stabilise the tetrameric form of M2PYK. In the absence of amino-acid ligands an apparent tetramer-monomer dissociation K d is estimated to be ~0...
May 10, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29746587/metabolic-reprogramming-of-kaposi-s-sarcoma-associated-herpes-virus-infected-b-cells-in-hypoxia
#19
Rajnish Kumar Singh, Fengchao Lang, Yonggang Pei, Hem Chandra Jha, Erle S Robertson
Kaposi's sarcoma associated herpesvirus (KSHV) infection stabilizes hypoxia inducible factors (HIFs). The interaction between KSHV encoded factors and HIFs plays a critical role in KSHV latency, reactivation and associated disease phenotypes. Besides modulation of large-scale signaling, KSHV infection also reprograms the metabolic activity of infected cells. However, the mechanism and cellular pathways modulated during these changes are poorly understood. We performed comparative RNA sequencing analysis on cells with stabilized hypoxia inducible factor 1 alpha (HIF1α) of KSHV negative or positive background to identify changes in global and metabolic gene expression...
May 10, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29743590/loss-of-function-of-ift88-determines-metabolic-phenotypes-in-thyroid-cancer
#20
Junguee Lee, Shinae Yi, Minho Won, Young Shin Song, Hyon-Seung Yi, Young Joo Park, Ki Cheol Park, Jung Tae Kim, Joon Young Chang, Min Joung Lee, Hae Joung Sul, Ji Eun Choi, Koon Soon Kim, Jukka Kero, Joon Kim, Minho Shong
Primary cilia are microtubule-based, dynamic organelles characterized by continuous assembly and disassembly. The intraflagellar transport (IFT) machinery, including IFT88 in cilia, is involved in the maintenance of bidirectional motility along the axonemes, which is required for ciliogenesis and functional competence. Cancer cells are frequently associated with loss of primary cilia and IFT functions. However, there is little information on the role of IFT88 or primary cilia in the metabolic remodeling of cancer cells...
May 10, 2018: Oncogene
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