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Regulated Alternative Translocation

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https://www.readbyqxmd.com/read/29771376/rna-dna-and-dna-dna-base-pairing-at-the-upstream-edge-of-the-transcription-bubble-regulate-translocation-of-rna-polymerase-and-transcription-rate
#1
Maria KIreeva, Cyndi Trang, Gayane Matevosyan, Joshua Turek-Herman, Vitaly Chasov, Lucyna Lubkowska, Mikhail Kashlev
Translocation of RNA polymerase (RNAP) along DNA may be rate-limiting for transcription elongation. The Brownian ratchet model posits that RNAP rapidly translocates back and forth until the post-translocated state is stabilized by NTP binding. An alternative model suggests that RNAP translocation is slow and poorly reversible. To distinguish between these two models, we take advantage of an observation that pyrophosphorolysis rates directly correlate with the abundance of the pre-translocated fraction. Pyrophosphorolysis by RNAP stabilized in the pre-translocated state by bacteriophage HK022 protein Nun was used as a reference point to determine the pre-translocated fraction in the absence of Nun...
May 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29731168/promoter-of-lncrna-gene-pvt1-is-a-tumor-suppressor-dna-boundary-element
#2
Seung Woo Cho, Jin Xu, Ruping Sun, Maxwell R Mumbach, Ava C Carter, Y Grace Chen, Kathryn E Yost, Jeewon Kim, Jing He, Stephanie A Nevins, Suet-Feung Chin, Carlos Caldas, S John Liu, Max A Horlbeck, Daniel A Lim, Jonathan S Weissman, Christina Curtis, Howard Y Chang
Noncoding mutations in cancer genomes are frequent but challenging to interpret. PVT1 encodes an oncogenic lncRNA, but recurrent translocations and deletions in human cancers suggest alternative mechanisms. Here, we show that the PVT1 promoter has a tumor-suppressor function that is independent of PVT1 lncRNA. CRISPR interference of PVT1 promoter enhances breast cancer cell competition and growth in vivo. The promoters of the PVT1 and the MYC oncogenes, located 55 kb apart on chromosome 8q24, compete for engagement with four intragenic enhancers in the PVT1 locus, thereby allowing the PVT1 promoter to regulate pause release of MYC transcription...
April 25, 2018: Cell
https://www.readbyqxmd.com/read/29650893/-towards-development-of-innovative-cancer-therapies-trans-omics-approach
#3
Reika Kawabata-Iwakawa, Masahiko Nishiyama
Comprehensive genomic and transcriptome analyses using next-generation sequencing(NGS)analysis has lead a discovery of a variety of novel driver gene mutations and new therapeutic targets for cancer patients, and has remarkably improved outcome of the patients through the development novel molecular targeting drugs. Even so, in so-called intractable or refractory cancers, those "druggable"alterations common to the diseases are rarely found due to the high diversity of the tumor. Furthermore, most of molecular target therapy is known to acquire the resistance to the drug by means of multiple factors such as up-regulation of the partially inhibited pathway, mutation of the target, activation of alternative pathways, histological translocation, and oncogene de-addiction...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29605770/p-coumaric-acid-mediated-protection-of-h9c2-cells-from-doxorubicin-induced-cardiotoxicity-involvement-of-augmented-nrf2-and-autophagy
#4
Mary Chacko Sunitha, Radhakrishnan Dhanyakrishnan, Bhaskara PrakashKumar, Kottayath Govindan Nevin
Doxorubicin (Dox) is a widely administered chemotherapeutic drug and incidences of cardiotoxicity associated with its administration have been of general concern. Extensive research proposes several mechanisms as a cause of Dox induced cardiotoxicity. However, none of these studies have been able to suggest a find one, cure all antidote for the same. To this end, several studies involving plant based compounds or natural products have gained acclaim for their ability to address at least one factor contributing to drug induced pathogenesis...
March 29, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29592970/spatio-temporal-map-kinase-dynamics-mediate-cell-behavior-coordination-during-fungal-somatic-cell-fusion
#5
Antonio Serrano, Julia Illgen, Ulrike Brandt, Nils Thieme, Anja Letz, Alexander Lichius, Nick Read, André Fleißner
Mitogen-activated protein kinases are conserved regulators of proliferation, differentiation and adaptation in eukaryotic cells. Their activity often involves changes in their subcellular localization, indicating an important role of these spatio-temporal dynamics for signal transmission. A striking model illustrating these dynamics is somatic cell fusion in Neurospora crassa Germinating spores of this fungus rapidly alternate between signal sending and receiving, thereby establishing a kind of cell-cell dialog, which involves the alternating membrane recruitment of the MAP kinase MAK-2 in both fusion partners...
March 28, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29588476/sequence-dependent-catalytic-regulation-of-the-spoiiie-motor-activity-ensures-directionality-of-dna-translocation
#6
Osvaldo Chara, Augusto Borges, Pierre-Emmanuel Milhiet, Marcelo Nöllmann, Diego I Cattoni
Transport of cellular cargo by molecular motors requires directionality to ensure proper biological functioning. During sporulation in Bacillus subtilis, directionality of chromosome transport is mediated by the interaction between the membrane-bound DNA translocase SpoIIIE and specific octameric sequences (SRS). Whether SRS regulate directionality by recruiting and orienting SpoIIIE or by simply catalyzing its translocation activity is still unclear. By using atomic force microscopy and single-round fast kinetics translocation assays we determined the localization and dynamics of diffusing and translocating SpoIIIE complexes on DNA with or without SRS...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29563102/protein-s-nitrosylation-controls-glycogen-synthase-kinase-3%C3%AE-function-independent-of-its-phosphorylation-state
#7
Sheng-Bing Wang, Vidya Venkatraman, Erin L Crowgey, Ting Liu, Zongming Fu, Ronald Holewinski, Mark Ranek, David A Kass, Brian O'Rourke, Jennifer E Van Eyk
RATIONALE: GSK-3β (glycogen synthase kinase 3β) is a multifunctional and constitutively active kinase known to regulate a myriad of cellular processes. The primary mechanism to regulate its function is through phosphorylation-dependent inhibition at serine-9 residue. Emerging evidence indicates that there may be alternative mechanisms that control GSK-3β for certain functions. OBJECTIVES: Here, we sought to understand the role of protein S -nitrosylation (SNO) on the function of GSK-3β...
May 25, 2018: Circulation Research
https://www.readbyqxmd.com/read/29556496/tet-enzymes-variants-and-differential-effects-on-function
#8
REVIEW
Philippa Melamed, Yahav Yosefzon, Cfir David, Anna Tsukerman, Lilach Pnueli
Discovery of the ten-eleven translocation 1 (TET) methylcytosine dioxygenase family of enzymes, nearly 10 years ago, heralded a major breakthrough in understanding the epigenetic modifications of DNA. Initially described as catalyzing the oxidation of methyl cytosine (5mC) to hydroxymethyl cytosine (5hmC), it is now clear that these enzymes can also catalyze additional reactions leading to active DNA demethylation. The association of TET enzymes, as well as the 5hmC, with active regulatory regions of the genome has been studied extensively in embryonic stem cells, although these enzymes are expressed widely also in differentiated tissues...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29556062/androgen-receptor-modulation-following-combination-exposure-to-brominated-flame-retardants
#9
Joubert Banjop Kharlyngdoh, Ajay Pradhan, Per-Erik Olsson
Endocrine disrupting compounds can interfere with androgen receptor (AR) signaling and disrupt steroidogenesis leading to reproductive failure. The brominated flame-retardant (BFR) 1, 2-dibromo-4-(1, 2-dibromoethyl) cyclohexane (TBECH), is an agonist to human, chicken and zebrafish AR. Recently another group of alternative BFRs, allyl 2, 4, 6-tribromophenyl ether (ATE), and 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether (DPTE) along with its metabolite 2-bromoallyl 2, 4, 6-tribromophenyl ether (BATE) were identified as potent human AR antagonists...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29555584/identification-of-two-stat3-variants-lacking-a-transactivation-domain-in-grass-carp-new-insights-into-alternative-splicing-in-the-modification-of-teleost-stat3-signaling
#10
Xinyan Wang, Linyong Du, He Wei, Anying Zhang, Kun Yang, Hong Zhou
Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT family in response to cytokines and growth factors. In mammals, alternative splicing of STAT3 generates STAT3α and STAT3β, which have distinct and overlapping functions. In the previous study, we have identified two spliceforms of Stat3α (Stat3α1 and Stat3α2) possessing all functional domains of Stat3 in grass carp (Ctenopharyngodon idella). In the present study, two Stat3β variants (Stat3β1 and Stat3β2) without C-terminal transactivation domain were isolated from this species, and their transcripts were ubiquitously expressed in all examined tissues with the highest levels in liver...
June 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29523552/the-lysine-299-residue-endows-the-multisubunit-mrp1-antiporter-with-dominant-roles-in-na-resistance-and-ph-homeostasis-in-corynebacterium-glutamicum
#11
Ning Xu, Yingying Zheng, Xiaochen Wang, Terry A Krulwich, Yanhe Ma, Jun Liu
Corynebacterium glutamicum is generally regarded as a moderately salt- and alkali-tolerant industrial organism. However, relatively little is known about the molecular mechanisms underlying these specific adaptations. Here, we found that the Mrp1 antiporter played crucial roles in conferring both environmental Na+ resistance and alkali tolerance whereas the Mrp2 antiporter was necessary in coping with high-KCl stress at alkaline pH. Furthermore, the Δ mrp1 Δ mrp2 double mutant showed the most-severe growth retardation and failed to grow under high-salt or alkaline conditions...
May 15, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29515442/ginkgolide-c-alleviates-myocardial-ischemia-reperfusion-induced-inflammatory-injury-via-inhibition-of-cd40-nf-%C3%AE%C2%BAb-pathway
#12
Rui Zhang, Dan Han, Zhenyu Li, Chengwu Shen, Yahui Zhang, Jun Li, Genquan Yan, Shasha Li, Bo Hu, Jiangbing Li, Ping Liu
Increasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion (MI/R) diseases. In this study, we investigated whether Ginkgolide C (GC), a potent anti-inflammatory flavone, extenuated MI/R injury through inhibition of inflammation. In vivo , rats with the occlusion of the left anterior descending (LAD) coronary artery were applied to mimic MI/R injury...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29506651/energetics-and-conformational-pathways-of-functional-rotation-in-the-multidrug-transporter-acrb
#13
Yasuhiro Matsunaga, Tsutomu Yamane, Tohru Terada, Kei Moritsugu, Hiroshi Fujisaki, Satoshi Murakami, Mitsunori Ikeguchi, Akinori Kidera
The multidrug transporter AcrB transports a broad range of drugs out of the cell by means of the proton-motive force. The asymmetric crystal structure of trimeric AcrB suggests a functionally rotating mechanism for drug transport. Despite various supportive forms of evidence from biochemical and simulation studies for this mechanism, the link between the functional rotation and proton translocation across the membrane remains elusive. Here, calculating the minimum free energy pathway of the functional rotation for the complete AcrB trimer, we describe the structural and energetic basis behind the coupling between the functional rotation and the proton translocation at atomic resolution...
March 6, 2018: ELife
https://www.readbyqxmd.com/read/29416846/pml-regulation-and-multifaceted-function-beyond-tumor-suppression
#14
REVIEW
Kuo-Sheng Hsu, Hung-Ying Kao
Promyelocytic leukemia protein (PML) was originally identified as a fusion partner of retinoic acid receptor alpha in acute promyelocytic leukemia patients with the (15;17) chromosomal translocation, giving rise to PML-RARα and RARα-PML fusion proteins. A body of evidence indicated that PML possesses tumor suppressing activity by regulating apoptosis, cell cycle, senescence and DNA damage responses. PML is enriched in discrete nuclear substructures in mammalian cells with 0.2-1 μm diameter in size, referred to as alternately Kremer bodies, nuclear domain 10, PML oncogenic domains or PML nuclear bodies (NBs)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29382730/translation-stress-positively-regulates-mscl-dependent-excretion-of-cytoplasmic-proteins
#15
Rosa Morra, Francesco Del Carratore, Howbeer Muhamadali, Luminita Gabriela Horga, Samantha Halliwell, Royston Goodacre, Rainer Breitling, Neil Dixon
The apparent mislocalization or excretion of cytoplasmic proteins is a commonly observed phenomenon in both bacteria and eukaryotes. However, reports on the mechanistic basis and the cellular function of this so-called "nonclassical protein secretion" are limited. Here we report that protein overexpression in recombinant cells and antibiotic-induced translation stress in wild-type Escherichia coli cells both lead to excretion of cytoplasmic protein (ECP). Condition-specific metabolomic and proteomic analyses, combined with genetic knockouts, indicate a role for both the large mechanosensitive channel (MscL) and the alternative ribosome rescue factor A (ArfA) in ECP...
January 30, 2018: MBio
https://www.readbyqxmd.com/read/29378013/a-conserved-structural-element-in-the-rna-helicase-upf1-regulates-its-catalytic-activity-in-an-isoform-specific-manner
#16
Manjeera Gowravaram, Fabien Bonneau, Joanne Kanaan, Vincent D Maciej, Francesca Fiorini, Saurabh Raj, Vincent Croquette, Hervé Le Hir, Sutapa Chakrabarti
The RNA helicase UPF1 is a key component of the nonsense mediated mRNA decay (NMD) pathway. Previous X-ray crystal structures of UPF1 elucidated the molecular mechanisms of its catalytic activity and regulation. In this study, we examine features of the UPF1 core and identify a structural element that adopts different conformations in the various nucleotide- and RNA-bound states of UPF1. We demonstrate, using biochemical and single molecule assays, that this structural element modulates UPF1 catalytic activity and thereby refer to it as the regulatory loop...
March 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29304433/probing-the-interaction-mechanisms-between-transmembrane-peptides-and-the-chaperonin-groel-with-fluorescence-anisotropy
#17
Xiaoqiang Wang, Han Chen, Xinwei Lu, Haixia Chi, Shixin Li, Fang Huang
Proper translocation, membrane insertion and folding are crucial biophysical steps in the biogenesis of functional transmembrane peptides/proteins (TMPs). ATP-dependent chaperonins are able to regulate each of these processes, but the underlying mechanisms remain unclear. In this work, interaction between the bacterial chaperonin GroEL and a synthetic fluorescent transmembrane peptide was investigated by fluorescence anisotropy. Binding of the peptide with GroEL resulted in increased fluorescence anisotropy and intensity...
April 5, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29246902/identification-of-the-integrin-binding-site-on-coagulation-factor-viia-required-for-proangiogenic-par2-signaling
#18
Andrea S Rothmeier, Enbo Liu, Sagarika Chakrabarty, Jennifer Disse, Barbara M Mueller, Henrik Østergaard, Wolfram Ruf
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease-activated receptor 2 (PAR2) that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor VIIa (FVIIa) elicits TF cytoplasmic domain-dependent proangiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin-binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1...
February 8, 2018: Blood
https://www.readbyqxmd.com/read/29246543/oncostatin-m-upregulates-hif-1%C3%AE-in-breast-tumor-associated-macrophages-independent-of-intracellular-oxygen-concentration
#19
Richa Shrivastava, Varsha Singh, Mohammad Asif, Mahendra Pal Singh Negi, Smrati Bhadauria
AIMS: HIF is an important transcription-regulator for adaptation to cellular stress in cells of myeloid origin. Classically, expression and activity of HIF1-α is regulated by oxygen-concentration within cell. However, there exists an alternative regulatory mechanism affecting HIF1-α levels independent of oxygen concentration particularly in inflammatory cells like macrophages. Here we report the mechanism of HIF1-α upregulation in TAMs by Oncostatin-M (OSM) independent of cellular oxygen concentration...
February 1, 2018: Life Sciences
https://www.readbyqxmd.com/read/29241544/dissociation-of-rad51-presynaptic-complexes-and-heteroduplex-dna-joints-by-tandem-assemblies-of-srs2
#20
Kyle Kaniecki, Luisina De Tullio, Bryan Gibb, Youngho Kwon, Patrick Sung, Eric C Greene
Srs2 is a superfamily 1 (SF1) helicase and antirecombinase that is required for genome integrity. However, the mechanisms that regulate Srs2 remain poorly understood. Here, we visualize Srs2 as it acts upon single-stranded DNA (ssDNA) bound by the Rad51 recombinase. We demonstrate that Srs2 is a processive translocase capable of stripping thousands of Rad51 molecules from ssDNA at a rate of ∼50 monomers/s. We show that Srs2 is recruited to RPA clusters embedded between Rad51 filaments and that multimeric arrays of Srs2 assemble during translocation on ssDNA through a mechanism involving iterative Srs2 loading events at sites cleared of Rad51...
December 12, 2017: Cell Reports
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