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https://www.readbyqxmd.com/read/29332244/structural-insights-into-the-function-of-elongator
#1
REVIEW
Udit Dalwadi, Calvin K Yip
Conserved from yeast to humans, Elongator is a protein complex implicated in multiple processes including transcription regulation, α-tubulin acetylation, and tRNA modification, and its defects have been shown to cause human diseases such as familial dysautonomia. Elongator consists of two copies of six core subunits (Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6) that are organized into two subcomplexes: Elp1/2/3 and Elp4/5/6 and form a stable assembly of ~ 850 kDa in size. Although the catalytic subunit of Elongator is Elp3, which contains a radical S-adenosyl-L-methionine (SAM) domain and a putative histone acetyltransferase domain, the Elp4/5/6 subcomplex also possesses ATP-modulated tRNA binding activity...
January 13, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29331577/a-novel-encystation-specific-protein-kinase-regulates-chitin-synthesis-in-entamoeba-invadens
#2
Sintu Kumar Samanta, Sneha Susan Varghese, Deepak Krishnan, Mithu Baidya, Digant Nayak, Sumanta Mukherjee, Sudip K Ghosh
Phosphorylation is an important post-translational modification of proteins and is involved in the regulation of a variety of cellular events. The proteome of Entamoeba invadens, the reptilian counterpart of Entamoeba histolytica consists of an overwhelming number of putative protein kinases, and some may have a role to play in Entamoeba encystation. In this study, we have identified a novel protein kinase named as EiCSpk (Entamoeba invadenscyst specific protein kinase) which expressed almost exclusively during encystation...
January 10, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29331521/increased-transcript-levels-and-kinetic-function-of-pyruvate-kinase-during-severe-dehydration-in-aestivating-african-clawed-frogs-xenopus-laevis
#3
Neal J Dawson, Yulia Biggar, Amal I Malik, Kenneth B Storey
The African clawed frog, Xenopus laevis, can withstand extremely arid conditions through aestivation, resulting in dehydration and urea accumulation. Aestivating X. laevis reduce their metabolic rate, and rely on anaerobic glycolysis to meet reduced ATP demands. The present study investigated how severe dehydration affected the transcript levels, kinetic profile, and phosphorylation state of the key glycolytic enzyme pyruvate kinase (PK) in the liver and skeletal muscle of X. laevis. Compared to control frogs, severely dehydrated frogs showed an increase in the transcript abundance of both liver and muscle isoforms of PK...
January 10, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29331071/hepatic-ppar%C3%AE-function-is-controlled-by-polyubiquitination-and-proteasome-mediated-degradation-via-the-coordinated-actions-of-paqr3-and-huwe1
#4
Zilong Zhao, Daqian Xu, Zheng Wang, Lin Wang, Ruomei Han, Zhenzhen Wang, Lujian Liao, Yan Chen
Peroxisome proliferator-activated receptor α (PPARα) is a key transcriptional factor that regulates hepatic lipid catabolism by stimulating fatty acid oxidation and ketogenesis in an adaptive response to nutrient starvation. However, how PPARα is regulated by post-translational modification is poorly understood. Here, we identified that PAQR3 promotes PPARα ubiquitination through the E3 ubiquitin ligase HUWE1, thereby negatively modulating PPARα functions both in vitro and in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid oxidation and ketogenesis upon fasting...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29330744/c-fos-downregulation-positively-regulates-epha5-expression-in-a-congenital-hypothyroidism-rat-model
#5
Honghua Song, Yuqin Zheng, Fuying Cai, Yanyan Ma, Jingyue Yang, Youjia Wu
The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites...
January 12, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29330435/beta-catenin-cleavage-enhances-transcriptional-activation
#6
Tatiana Goretsky, Emily M Bradford, Qing Ye, Olivia F Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C Keller, Preetika Sinh, Josep M Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A Barrett
Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330049/the-histone-demethylase-phf8-promotes-adult-acute-lymphoblastic-leukemia-through-interaction-with-the-mek-erk-signaling-pathway
#7
Yue Fu, Yaling Yang, Xiaoming Wang, Xiaolin Yin, Minran Zhou, Siqi Wang, Lin Yang, Tao Huang, Man Xu, Chunyan Chen
Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29326300/relationship-between-histone-modifications-and-transcription-factor-binding-is-protein-family-specific
#8
Beibei Xin, Remo Rohs
The very small fraction of putative binding sites (BSs) that are occupied by transcription factors (TFs) in vivo can be highly variable across different cell types. This observation has been partly attributed to changes in chromatin accessibility and histone modification (HM) patterns surrounding BSs. Previous studies focusing on BSs within DNA regulatory regions found correlations between HM patterns and TF binding specificities. However, a mechanistic understanding of TF-DNA binding specificity determinants is still not available...
January 11, 2018: Genome Research
https://www.readbyqxmd.com/read/29326161/sumo2-3-modification-of-activating-transcription-factor-5-atf5-controls-its-dynamic-translocation-at-the-centrosome
#9
Yunsheng Yuan, Kari Gaither, Eugene Kim, Edward Liu, Ming Hu, Kathy Lengel, Dongmeng Qian, Yidi Xu, Bin Wang, Henning Knipprath, David Liu
Activating transcription factor 5 (ATF5) is a member of the ATF/CREB family of transcription factors. ATF5 regulates stress responses and cell survival, proliferation, and differentiation and also plays a role in viral infections, cancer, diabetes, schizophrenia, and the olfactory system. Moreover, it was found to also have a critical, cell cycle-dependent structural function at the centrosome. However, the mechanism that controls ATF5's localization at the centrosome is unclear. Here, we report that ATF5 is SUMO2/3- modified at a conserved SUMO-targeting consensus site in various types of mammalian cells...
January 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29326075/use-of-crispr-cas9-gene-editing-tools-for-developing-models-in-drug-discovery
#10
REVIEW
Gulzar Ahmad, Mansoor Amiji
Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9 (CRISPR/Cas9) enables targeted genome engineering. The simplicity of this system, its facile engineering, and amenability to multiplex genes make it the system of choice for many applications. This system has revolutionized our ability to carry out gene editing, transcription regulation, genome imaging, and epigenetic modification. In this review, we discuss the discovery of CRISPR/Cas9, its mechanism of action, its application in medicine and animal model development, and its delivery...
January 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29325877/dmcatd-a-cathepsin-d-like-peptidase-of-the-hematophagous-insect-dipetalogaster-maxima-hemiptera-reduviidae-purification-bioinformatic-analyses-and-the-significance-of-its-interaction-with-lipophorin-in-the-internalization-by-developing-oocytes
#11
Jimena Leyria, Leonardo L Fruttero, Rodrigo Ligabue-Braun, Marina S Defferrari, Estela L Arrese, José L Soulages, Beatriz P Settembrini, Celia R Carlini, Lilián E Canavoso
DmCatD, a cathepsin D-like peptidase of the hematophagous insect Dipetalogaster maxima, is synthesized by the fat body and the ovary and functions as yolk protein precursor. Functionally, DmCatD is involved in vitellin proteolysis. In this work, we purified and sequenced DmCatD, performed bioinformatic analyses and investigated the events involved in its targeting and storage in developing oocytes. By ion exchange and gel filtration chromatography, DmCatD was purified from egg homogenates and its identity was confirmed by mass spectrometry...
January 8, 2018: Journal of Insect Physiology
https://www.readbyqxmd.com/read/29325627/epigenetic-mechanisms-underlying-nervous-system-diseases
#12
Irfan A Qureshi, Mark F Mehler
Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29325176/dynamic-motif-occupancy-dynamo-analysis-identifies-transcription-factors-and-their-binding-sites-driving-dynamic-biological-processes
#13
Zheng Kuang, Zhicheng Ji, Jef D Boeke, Hongkai Ji
Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data...
January 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29323256/splicing-of-platelet-resident-pre-mrnas-upon-activation-by-physiological-stimuli-results-in-functionally-relevant-proteome-modifications
#14
Giovanni Nassa, Giorgio Giurato, Giovanni Cimmino, Francesca Rizzo, Maria Ravo, Annamaria Salvati, Tuula A Nyman, Yafeng Zhu, Mattias Vesterlund, Janne Lehtiö, Paolo Golino, Alessandro Weisz, Roberta Tarallo
Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320743/a-p300-and-sirt1-regulated-acetylation-switch-of-c-ebp%C3%AE-controls-mitochondrial-function
#15
Mohamad A Zaini, Christine Müller, Tristan V de Jong, Tobias Ackermann, Götz Hartleben, Gertrud Kortman, Karl-Heinz Gührs, Fabrizia Fusetti, Oliver H Krämer, Victor Guryev, Cornelis F Calkhoven
Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other physiological processes...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29319347/sigma-factors-mediated-signaling-in-mycobacterium-tuberculosis
#16
Peifu Zhou, Xinpeng Wang, Yuzhong Zhao, Wei Yuan, Jianping Xie
Activation of signaling cascades is critical for Mycobacterium tuberculosis (Mtb) to adapt the macrophage lifestyle. Parallel to several signal systems, sigma factor systems, especially the extra-cytoplasmic function sigma factors, are crucial for Mtb signaling. Most sigma factors lack a signal sensory domain and often are activated by various proteins that perceive the environmental cues and relay the signals through variegated post-translational modifications via the activity of antisigma factor, protein kinase and related transcriptional regulators...
January 10, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29318497/epigenetic-mechanism-of-survivin-dysregulation-in-human-cancer
#17
REVIEW
Hui Lyu, Jingcao Huang, Zhimin He, Bolin Liu
Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Because of its selective expression in tumor, but not normal tissues, Survivin has been recognized as an attractive target for cancer treatment...
January 4, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29317751/methylation-in-mycobacterium-tuberculosis-is-lineage-specific-with-associated-mutations-present-globally
#18
Jody Phelan, Paola Florez de Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L Bergval, Richard Anthony, Ruth McNerney, Martin Antonio, Isabel Portugal, Miguel Viveiros, Susana Campino, Martin L Hibberd, Taane G Clark
DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316981/host-specific-differences-in-the-response-of-cultured-macrophages-to-campylobacter-jejuni-capsule-and-o-methyl-phosphoramidate-mutants
#19
Sungwon Kim, Andrea Vela, Sara M Clohisey, Spiridoula Athanasiadou, Pete Kaiser, Mark P Stevens, Lonneke Vervelde
Campylobacter jejuni is the leading cause of bacterial food-borne gastroenteritis worldwide and human infections are frequently associated with handling and consumption of contaminated poultry. The polysaccharide capsule of C. jejuni plays important roles in colonisation of the chicken gut, invasion of epithelial cells and serum resistance and is subject to modification with O-methyl phosphoramidate (MeOPN) in most strains. In this study, the cytokine responses of mouse bone marrow-derived macrophages (mBMMs), chicken bone marrow-derived macrophages (chBMMs) and human monocyte-derived macrophages (hMDMs) were measured following infection with C...
January 9, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29316891/serum-mir-486-5p-as-a-diagnostic-marker-in-cervical-cancer-with-investigation-of-potential-mechanisms
#20
Chunmei Li, Xiaojiao Zheng, Wei Li, Fumao Bai, Jianxin Lyu, Qing H Meng
BACKGROUND: Around the world, cervical cancer is the fourth most common cancer among women. MicroRNAs (miRNAs) and agents that target mRNAs have been introduced as novel diagnostic markers and therapeutic approaches, respectively, in cancer. MiRNA-486-5p is a candidate regulator of phosphatase and tensin homolog (PTEN) in silico, and the downregulation of PTEN in cervical cancer is not consistent with its mutation, which suggests that PTEN may be subjected to post-transcription modification moderated by miRNAs...
January 9, 2018: BMC Cancer
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