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FEBS Journal

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https://www.readbyqxmd.com/read/29323792/the-retinamide-vnlg-152-inhibits-ar-ar-v7-and-mnk-eif4esignaling-pathways-to-suppress-emt-and-castration-resistant-prostate-cancer-xenograft-growth
#1
Vidya P Ramamurthy, Senthilmurugan Ramalingam, Lalji K Gediya, Vincent C O Njar
VNLG-152, a lead novel retinamide (NR) shown to suppress growth and progression in genetically diverse PCa cells via inhibition of AR signaling and eIF4E translational machinery. Herein, we report therapeutic effects of VNLG-152 on castration resistant prostate cancer (CRPC) growth and metastatic phenotype in CRPC tumor xenograft model. Administration of VNLG-152 significantly and dose-dependently suppressed the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% respectively (P = 0.001), vs. vehicle with no host toxicity...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29323787/inhibition-of-uvssa-ubiquitination-suppresses-transcription-coupled-nucleotide-excision-repair-deficiency-caused-by-dissociation-from-usp7
#2
Mitsuru Higa, Kiyoji Tanaka, Masafumi Saijo
Transcription-coupled nucleotide excision repair (TC-NER) is a subpathway of nucleotide excision repair that efficiently removes transcription-blocking DNA damage from the transcribed strands of active genes. UVSSA is a causative gene for UV-sensitive syndrome (UVS S), which is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in TC-NER. UV-stimulated scaffold protein A (UVSSA), the product of UVSSA, forms a complex with ubiquitin-specific peptidase 7 (USP7) and is stabilized by interaction with USP7...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29323786/pulmonary-endoplasmic-reticulum-stress-scars-smoke-and-suffocation
#3
REVIEW
Jennifer A Dickens, Elke Malzer, Joseph E Chambers, Stefan J Marciniak
Protein misfolding within the endoplasmic reticulum (ER stress) can be a cause or consequence of pulmonary disease. Mutation of proteins restricted to the alveolar type II pneumocyte can lead to inherited forms of pulmonary fibrosis, but even sporadic cases of pulmonary fibrosis appear to be strongly associated with activation of the unfolded protein response (UPR) and/or the integrated stress response (ISR). Inhalation of smoke can impair protein folding and may be an important cause of pulmonary ER stress...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29323785/crystal-structure-of-the-dna-binding-domain-of-the-lysr-type-transcriptional-regulator-cbnr-in-complex-with-a-dna-fragment-of-the-recognition-binding-site-in-the-promoter-region
#4
Maharani Pertiwi Koentjoro, Naruhiko Adachi, Miki Senda, Naoto Ogawa, Toshiya Senda
LysR-type transcriptional regulators (LTTRs) are among the most abundant transcriptional regulators in bacteria. CbnR is an LTTR derived from Cupriavidus necator (formerly Alcaligenes eutrophus or Ralstonia eutropha) NH9 and is involved in transcriptional activation of the cbnABCD genes encoding chlorocatechol degradative enzymes. CbnR interacts with a cbnA promoter region of approximately 60 bp in length that contains the recognition binding site (RBS) and activation binding site (ABS). Upon inducer binding, CbnR seems to undergo conformational changes, leading to activation of the transcription...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29323772/the-role-of-nrf2-signaling-in-counteracting-neurodegenerative-diseases
#5
REVIEW
Albena T Dinkova-Kostova, Rumen V Kostov, Aleksey G Kazantsev
The transcription factor Nrf2 (nuclear factor erythroid 2 p45-related factor 2) functions at the interface of cellular redox and intermediary metabolism. Nrf2 target genes encode antioxidant enzymes, and proteins involved in xenobiotic detoxification, repair and removal of damaged proteins and organelles, inflammation, and mitochondrial bioenergetics. The function of Nrf2 is altered in many neurodegenerative disorders, such as Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis and Friedreich's ataxia...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29288533/challenges-to-dna-replication-in-hypoxic-conditions
#6
REVIEW
Natalie Ng, Karin Purshouse, Iosifina P Foskolou, Monica M Olcina, Ester M Hammond
The term hypoxia refers to any condition where insufficient oxygen is available and therefore encompasses a range of actual oxygen concentrations. The regions of tumours adjacent to necrotic areas are at almost anoxic levels and are known to be extremely therapy resistant (radiobiological hypoxia). The biological response to radiobiological hypoxia includes the rapid accumulation of replication stress and subsequent DNA damage response, including both ATR and ATM-mediated signalling, despite the absence of detectable DNA damage...
December 30, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29288530/pka-binding-domain-of-akap8-is-essential-for-direct-interaction-with-dpy30-protein
#7
Anna Bieluszewska, Martyna Weglewska, Tomasz Bieluszewski, Krzysztof Lesniewicz, Elzbieta Poreba
The main function of the A kinase-anchoring proteins (AKAPs) is to target the cAMP-dependent protein kinase A (PKA) to its cellular substrates through the interaction with its regulatory subunits. Besides anchoring of PKA, AKAP8 participates in regulating the H3K4 histone methyltransferase (HMT) complexes. It is also involved in DNA replication, apoptosis, transcriptional silencing of rRNA genes, alternative splicing, and chromatin condensation during mitosis. In this study, we focused on the interaction between AKAP8 and the core subunit of all known H3K4 HMT complexes-DPY30 protein...
December 30, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29284196/genome-wide-survey-and-phylogenetic-analysis-of-histone-acetyltransferases-and-histone-deacetylases-of-plasmodium-falciparum
#8
REVIEW
Abhishek Kanyal, Mukul Rawat, Pratima Gurung, Deepak Choubey, Krishanpal Anamika, Krishanpal Karmodiya
Malaria parasites can readily sense and adapt to environmental changes, thus making the control and eradication of this disease difficult. Molecular studies have unraveled a very tightly coordinated transcriptional machinery governed by complex regulatory mechanisms including chromatin modification and spatiotemporal compartmentalization. Histone modifying enzymes play key roles in the regulation of chromatin modification and gene expression, which are associated with cell cycle progression, antigenic variation and immune evasion...
December 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29283511/structural-plasticity-of-mini-m-conotoxins-expression-of-all-mini-m-subtypes-by-conus-regius
#9
Aldo Franco, Sanaz Dovell, Carolina Moller, Meghan Grandal, Evan Clark, Frank Marí
The mini-M conotoxins are peptidic scaffolds found in the venom of cones snails. These scaffolds are tightly folded structures held together by three disulfide bonds with a CC-C-C-CC arrangement (conotoxin framework III) and belong to the M Superfamily of conotoxins. Here we describe twenty-five mini-M conotoxins from the venom of Conus regius, a Western Atlantic worm-hunting cone snail species using transcriptomic and peptidomic analyses. These C. regius conotoxins belong to three different subtypes: M1, M2, and M3...
December 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29283500/identification-of-a-novel-nucleophosmin-interaction-motif-in-the-tumor-suppressor-p14arf
#10
Enrico Luchinat, Sara Chiarella, Mimma Franceschini, Adele Di Matteo, Maurizio Brunori, Lucia Banci, Luca Federici
The tumor suppressor p14arf interacts, in response to oncogenic signals, with the p53 E3-ubiquitin ligase HDM2, thereby resulting in p53 stabilization and activation. In addition, it also exerts tumor suppressive functions in p53-independent contexts. The activities of p14arf are regulated by the nucleolar chaperone nucleophosmin (NPM1), which controls its levels and cellular localization. In acute myeloid leukemia with mutations in the NPM1 gene, mutated NPM1 aberrantly translocates in the cytosol carrying with itself p14arf that is subsequently degraded, thus impairing the p14arf-HDM2-p53 axis...
December 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29282902/construction-of-green-fluorescence-protein-mutant-to-monitor-stt3b-dependent-n-glycosylation
#11
Toshihiko Kitajima, Wei Xue, Yi-Shi Liu, Chun-Di Wang, Si-Si Liu, Morihisa Fujita, Xiao-Dong Gao
Oligosaccharyltransferases (OSTs) mediate the en bloc transfer of N-glycan intermediates onto the asparagine residue in glycosylation sequons (N-X-S/T, X≠P). These enzymes are typically heteromeric complexes composed of several membrane-associated subunits, in which STT3 is highly conserved as a catalytic core. Metazoan organisms encode two STT3 genes (STT3A and STT3B) in their genome, resulting in the formation of at least two distinct OST isoforms consisting of shared subunits and complex specific subunits...
December 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29282865/membrane-localization-of-a-myb3-transcription-factor-regulated-by-a-tvcyp1-cyclophilin-in-the-parasitic-protozoan-trichomonas-vaginalis
#12
Chien-Hsin Chu, Yu-Hsin Huang, Hsing-Wei Liu, Hong-Ming Hsu, Jung-Hsiang Tai
In Trichomonas vaginalis, a TvCyP1 cyclophilin was previously demonstrated to regulate the nuclear translocation of Myb1 and Myb3, which respectively repress and activate transcription of an adhesion protein ap65-1 gene. In the present study, TvCyP1 was found to bind to Myb3 at sites spanning 54 Gly-Pro55 and 72 Gly-Pro73 with differential affinities. When Gly54 and Gly72 in Myb3 were both mutated, the mutant protein was restrained on outer membranes of hydrogenosomes and some cytoplasmic vesicles. In purified Myb3 protein complex, a high-molecular-weight Myb3-interacting protein (Myb3IPhmw ) and a 72-kDa heat shock protein (TvHSP72) were identified and characterized, with direct binding of Myb3 to Myb3IPhmw and TvHSP72 confirmed in vitro...
December 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29281179/a-high-parasite-density-environment-induces-transcriptional-changes-and-cell-death-in-plasmodium-falciparum-blood-stages
#13
Evelyn S Chou, Sabia Z Abidi, Marian Teye, Aleksandra Leliwa-Sytek, Thomas S Rask, Simon A Cobbold, Gerry Q Tonkin-Hill, Krishanthi S Subramaniam, Anna E Sexton, Darren J Creek, Johanna P Daily, Michael F Duffy, Karen P Day
Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans. This species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria population size as a mechanism to possibly explain these in vivo observations. Specifically, P. falciparum blood stages from a high but not low-density environment exhibited unique phenotypic changes during the late trophozoite and schizont stages of the intraerythrocytic cycle...
December 27, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29278453/functional-role-of-the-core-gap-in-the-middle-part-of-tropomyosin
#14
Alexander M Matyushenko, Daniil V Shchepkin, Galina V Kopylova, Sergey Y Bershitsky, Natalia A Koubassova, Andrey K Tsaturyan, Dmitrii I Levitsky
Tropomyosin (Tpm) is an α-helical coiled-coil actin-binding protein playing an essential role in the regulation of muscle contraction. The middle part of the Tpm molecule has some specific features, such as the presence of non-canonical residues as well as a substantial gap at the interhelical interface, which are believed to destabilize coiled-coil and impart structural flexibility to this part of the molecule. To study how the gap affects structural and functional properties of α-striated Tpm (Tpm1.1 isoform that is expressed in cardiac and skeletal muscles) we substituted large conserved apolar core residues located at both sides of the gap with smaller ones by mutations M127A/I130A and M141A/Q144A...
December 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29278448/a-stereospecific-carboxyl-esterase-from-bacillus-coagulans-hosting-non-lipase-activity-within-a-lipase-like-fold
#15
Valerio De Vitis, Cristina Nakhnoukh, Andrea Pinto, Martina Letizia Contente, Alberto Barbiroli, Mario Milani, Martino Bolognesi, Francesco Molinari, Louise J Gourlay, Diego Romano
Microbial carboxylesterases are important biocatalysts that selectively hydrolyze an extensive range of esters. Here, we report the biochemical and structural characterization of an atypical carboxylesterase from Bacillus coagulans (BCE), endowed with high enantioselectivity towards different 1,2-O-isopropylideneglycerol (IPG or solketal) esters. BCE efficiently catalyzes the production of enantiopure (S)-IPG, a chiral building block for the synthesis of β-blockers, glycerophospholipids and prostaglandins; efficient hydrolysis was observed up to 65°C...
December 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29265728/impaired-muscle-relaxation-and-mitochondrial-fission-associated-with-genetic-ablation-of-cytoplasmic-actin-isoforms
#16
Allison R O'Rourke, Angus Lindsay, Michael D Tarpey, Samantha Yuen, Preston McCourt, D'anna M Nelson, Benjamin J Perrin, David D Thomas, Espen E Spangenburg, Dawn A Lowe, James M Ervasti
While αsk -actin isoforms predominate in adult striated muscle, skeletal muscle-specific knockouts of non-muscle cytoplasmic βcyto - or γcyto -actin each cause a mild, but progressive myopathy affected by an unknown mechanism. Using transmission electron microscopy, we identified morphological abnormalities in both the mitochondria and the sarcoplasmic reticulum in aged muscle-specific βcyto - and γcyto -actin knockout mice. We found βcyto - and γcyto -actin proteins to be enriched in isolated mitochondrial associated membrane preparations, which represent the interface between mitochondria and sarco-endoplasmic reticulum important in signaling and mitochondrial dynamics...
December 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29253316/inositol-1-4-5-trisphosphate-receptors-and-neurodegenerative-disorders
#17
REVIEW
Polina A Egorova, Ilya B Bezprozvanny
Inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular ion channel that mediates the release of calcium ions from the endoplasmic reticulum (ER). IP3R plays a role in basic biological functions, such as cell division, differentiation, fertilization, and cell death; and is involved in developmental processes including learning, memory, and behavior. Deregulation of neuronal calcium signaling results in disturbance of cell homeostasis, synaptic loss and dysfunction, eventually leading to cell death...
December 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29247468/the-f1-atpase-from-trypanosoma-brucei-is-elaborated-by-three-copies-of-an-additional-p18-subunit
#18
Ondřej Gahura, Karolína Šubrtová, Hana Váchová, Brian Panicucci, Ian M Fearnley, Michael E Harbour, John E Walker, Alena Zíková
The F-ATPases (also called the F1 Fo -ATPases or ATP synthases) are multi-subunit membrane-bound molecular machines that produce ATP in bacteria and in eukaryotic mitochondria and chloroplasts. The structures and enzymic mechanisms of their F1 -catalytic domains are highly conserved in all species investigated hitherto. However, there is evidence that the F-ATPases from the group of protozoa known as Euglenozoa have novel features. Therefore, we have isolated pure and active F1 -ATPase from the euglenozoan parasite, Trypanosoma brucei, and characterized it...
December 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29240300/genomic-origin-and-nuclear-localization-of-terra-telomeric-repeat-containing-rna-from-darkness-to-dawn
#19
REVIEW
Aurélie Diman, Anabelle Decottignies
Long non-coding RNAs, produced from distinct regions of the chromosomes, are emerging as new key players in several important biological processes. The long non-coding RNAs add a new layer of complexity to cellular regulatory pathways, from transcription to cellular trafficking or chromatin remodeling. More than 25 years ago, the discovery of a transcriptional activity at telomeres of protozoa ended the long-lasting belief that telomeres were transcriptionally silent. Since then, progressively accumulating evidences established that production of TElomeric Repeat-containing RNA (TERRA) was a general feature of eukaryotic cells...
December 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29240297/shared-cam-and-s100a1-binding-epitopes-in-the-distal-trpm4-n-terminus
#20
Kristyna Bousova, Petr Herman, Jaroslav Vecer, Lucie Bednarova, Lenka Monincova, Pavel Majer, Ladislav Vyklicky, Jiri Vondrasek, Jan Teisinger
The transient receptor potential channel of melastatin 4 (TRPM4) belongs to a group of large ion receptors that are involved in countless cell signalling cascades. This unique member is ubiquitously expressed in many human tissues, especially in cardiomyocytes, where it plays an important role in cardiovascular processes. Transient receptor potential channels (TRPs) are usually constituted by intracellular N- and C- termini, which serve as mediators affecting allosteric modulation of channels, resulting in the regulation of the channel function...
December 14, 2017: FEBS Journal
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