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Tubulin

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https://www.readbyqxmd.com/read/27926524/selective-hdac-inhibition-by-acy-241-enhances-the-activity-of-paclitaxel-in-solid-tumor-models
#1
Pengyu Huang, Ingrid Almeciga-Pinto, Matthew Jarpe, John H van Duzer, Ralph Mazitschek, Min Yang, Simon S Jones, Steven N Quayle
ACY-241 is a novel, orally available and selective histone deacetylase (HDAC) 6 inhibitor in Phase 1b clinical development in multiple myeloma (NCT 02400242). Like the structurally related drug ACY-1215 (ricolinostat), ACY-241 has the potential for a substantially reduced side effect profile versus current nonselective HDAC inhibitor drug candidates due to reduced potency against Class I HDACs while retaining the potential for anticancer effectiveness. We now show that combination treatment of xenograft models with paclitaxel and either ricolinostat or ACY-241 significantly suppresses solid tumor growth...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923412/effects-of-vitrification-on-blastomere-viability-and-cytoskeletal-integrity-in-mouse-embryos
#2
Zenon Oikonomou, Katerina Chatzimeletiou, Antonia Sioga, Louisa Oikonomou, Basil C Tarlatzis, Efstratios Kolibianakis
Vitrification is widely used to cryopreserve supernumerary embryos following in vitro fertilization (IVF). The mouse model was used to investigate the effects of vitrification on blastomere viability, using viability markers, and on the cytoskeleton, by analysing spindle/chromosome configurations, using confocal scanning microscopy. Ninety cleavage and morula stage dimethyl sulphoxide (DMSO)/EG vitrified mouse embryos were either processed immediately following warming for viability assessment by labelling with the fluorescent markers carboxyfluorescein-diacetate succinimidylester (CFSE) and propidium iodide (PI) or were cultured to the blastocyst stage and immunostained with α-tubulin antibody to visualize microtubules and DAPI or PI to visualize DNA...
December 7, 2016: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/27922059/protein-self-assembly-onto-nanodots-leads-to-formation-of-conductive-bio-based-hybrids
#3
Xiao Hu, Chenbo Dong, Rigu Su, Quan Xu, Cerasela Zoica Dinu
The next generation of nanowires that could advance the integration of functional nanosystems into synthetic applications from photocatalysis to optical devices need to demonstrate increased ability to promote electron transfer at their interfaces while ensuring optimum quantum confinement. Herein we used the biological recognition and the self-assembly properties of tubulin, a protein involved in building the filaments of cellular microtubules, to create stable, free standing and conductive sulfur-doped carbon nanodots-based conductive bio-hybrids...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920216/mozart1-and-%C3%AE-tubulin-complex-receptors-are-both-required-to-turn-%C3%AE-tusc-into-an-active-microtubule-nucleation-template
#4
Tien-Chen Lin, Annett Neuner, Dirk Flemming, Peng Liu, Takumi Chinen, Ursula Jäkle, Robert Arkowitz, Elmar Schiebel
MOZART1/Mzt1 is required for the localization of γ-tubulin complexes to microtubule (MT)-organizing centers from yeast to human cells. Nevertheless, the molecular function of MOZART1/Mzt1 is largely unknown. Taking advantage of the minimal MT nucleation system of Candida albicans, we reconstituted the interactions of Mzt1, γ-tubulin small complex (γ-TuSC), and γ-tubulin complex receptors (γ-TuCRs) Spc72 and Spc110 in vitro. With affinity measurements, domain deletion, and swapping, we show that Spc110 and Mzt1 bind to distinct regions of the γ-TuSC...
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27918450/janus-compounds-5-chloro-n%C3%A2-methyl-n%C3%A2-aryl-9h-pyrimido-4-5-b-indole-2-4-diamines-cause-both-microtubule-depolymerizing-and-stabilizing-effects
#5
Cristina C Rohena, April L Risinger, Ravi Kumar Vyas Devambatla, Nicholas F Dybdal-Hargreaves, Roma Kaul, Shruti Choudhary, Aleem Gangjee, Susan L Mooberry
While evaluating a large library of compounds designed to inhibit microtubule polymerization, we identified four compounds that have unique effects on microtubules. These compounds cause mixed effects reminiscent of both microtubule depolymerizers and stabilizers. Immunofluorescence evaluations showed that each compound initially caused microtubule depolymerization and, surprisingly, with higher concentrations, microtubule bundles were also observed. There were subtle differences in the propensity to cause these competing effects among the compounds with a continuum of stabilizing and destabilizing effects...
December 2, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27916523/localized-mechanical-stress-promotes-microtubule-rescue
#6
Hélène de Forges, Antoine Pilon, Isabelle Cantaloube, Antoine Pallandre, Anne-Marie Haghiri-Gosnet, Franck Perez, Christian Poüs
Microtubule dynamics rely on the properties of tubulin and are regulated by microtubule-associated proteins. GTP-tubulin assembles into hollow polymers, which can depolymerize upon GTP hydrolysis. Depolymerizing microtubules may stop shrinking and resume growth. Such rescues are regulated by microtubule-associated proteins like CLIP-170 and the CLASPs [1, 2]. Microtubule domains prone to rescues contain discrete regions (previously termed "GTP islands") that retain a GTP-tubulin-like conformation in the main body of the microtubule [3]...
November 22, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27916024/neuron-specific-expression-of-p48-ebp1-during-murine-brain-development-and-its-contribution-to-cns-axon-regeneration
#7
Hyo Rim Ko, Inwoo Hwang, So Yoon Chang, Yun Sil Kim, Won Soon Park, Jee-Yin Ahn
P48 Ebp1 is expressed in rapidly proliferating cells such as cancer cells and accelerates cell growth and survival. However, its expression pattern and role in central nervous system development have not been studied. Here, we demonstrated the spatiotemporal expression pattern of p48 Ebp1 during embryonic development and the postnatal period. During embryonic development, p48 Ebp1 was highly expressed in the brain. Expression gradually decreased after birth but was still more abundant than p42 expression after birth...
December 5, 2016: BMB Reports
https://www.readbyqxmd.com/read/27915305/dna-barcoding-coupled-with-high-resolution-melting-analysis-enables-rapid-and-accurate-distinction-of-aspergillus-species
#8
Gabor Fidler, Sandor Kocsube, Eva Leiter, Sandor Biro, Melinda Paholcsek
We describe a high-resolution melting (HRM) analysis method that is rapid, reproducible, and able to identify reference strains and further 40 clinical isolates of Aspergillus fumigatus (14), A. lentulus (3), A. terreus (7), A. flavus (8), A. niger (2), A. welwitschiae (4), and A. tubingensis (2). Asp1 and Asp2 primer sets were designed to amplify partial sequences of the Aspergillus benA (beta-tubulin) genes in a closed-, single-tube system. Human placenta DNA, further Aspergillus (3), Candida (9), Fusarium (6), and Scedosporium (2) nucleic acids from type strains and clinical isolates were also included in this study to evaluate cross reactivity with other relevant pathogens causing invasive fungal infections...
December 3, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27915168/interactions-of-long-chain-homologues-of-colchicine-with-tubulin
#9
Ana Marzo-Mas, Pascale Barbier, Gilles Breuzard, Diane Allegro, Eva Falomir, Juan Murga, Miguel Carda, Vincent Peyrot, J Alberto Marco
Several colchicine analogues in which the N-acetyl residue has been replaced by aliphatic, straight-chain acyl moieties, have been synthesized. These compounds show high cytotoxic activity at the nanomolar level against the tumoral cell lines HT-29, MCF-7 and A549. Some of them exhibit activities in the picomolar range against the HT-29 line and are thus two to three orders of magnitude more cytotoxic than colchicine. In this specific cell line, the activities were found to be closely related to the length of the acyl carbon chain, an increase in the latter giving rise to an increase in the cytotoxicity with a maximum in the range of 10-12 carbon atoms, followed by a decrease in activity with still longer chains...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27915054/curdione-attenuates-thrombin-induced-human-platelet-activation-%C3%AE-1-tubulin-as-a-potential-therapeutic-target
#10
Dongling Zhang, Wenhao Qiao, Yingli Zhao, Hui Fang, Dujuan Xu, Quan Xia
Rhizoma Curcumae, the dry rhizomes derived from Curcuma aromatica Salisb., are a classical Chinese medicinal herb used to activate blood circulation, remove blood stasis and alleviate pain. Our previous study proved that curdione, a sesquiterpene compound isolated from the essential oil of Curcuma aromatica Salisb. can inhibit platelet activation suggesting its significant anticoagulant and antithrombotic effects. However, the underlying mechanism of curdione mediated anti-platelet effect has not been fully elucidated...
November 30, 2016: Fitoterapia
https://www.readbyqxmd.com/read/27915037/quantification-of-pea-enation-mosaic-virus-1-and-2-during-infection-of-pisum-sativum-by-one-step-real-time-rt-pcr
#11
Juliette Doumayrou, Melissa Sheber, Bryony C Bonning, W Allen Miller
Pea enation mosaic virus 1 (PEMV1) and Pea enation mosaic virus 2 (PEMV2) are two viruses in an obligate symbiosis that cause pea enation mosaic disease mainly in plants in the Fabaceae family. This virus system is a valuable model to investigate plant virus replication, movement and vector transmission. Thus, here we describe growth conditions, virus detection methods, and virus accumulation behavior. To measure the accumulation and movement of PEMV1 and PEMV2 in plants during the course of infection, we developed a quantitative real-time one-step reverse transcription PCR procedure using the SYBR-green(®) technology...
November 30, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27915022/concentration-dependent-survival-and-neural-differentiation-of-murine-embryonic-stem-cells-cultured-on-polyethylene-glycol-dimethacrylate-hydrogels-possessing-a-continuous-concentration-gradient-of-n-cadherin-derived-peptide-his-ala-val-asp-lle
#12
Hyun Ju Lim, Matthew C Mosley, Yuki Kurosu, Laura A Smith Callahan
: N-cadherin cell-cell signaling plays a key role in the structure and function of the nervous system. However, few studies have incorporated bioactive signaling from n-cadherin into tissue engineering matrices. The present study uses a continuous gradient approach in polyethylene glycol dimethacrylate hydrogels to identify concentration dependent effects of n-cadherin peptide, His-Ala-Val-Asp-Lle (HAVDI), on murine embryonic stem cell survival and neural differentiation. The n-cadherin peptide was found to affect the expression of pluripotency marker, alkaline phosphatase, in murine embryonic stem cells cultured on n-cadherin peptide containing hydrogels in a concentration dependent manner...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27912174/synthesis-and-cytostatic-properties-of-polyfunctionalized-furanoallocolchicinoids
#13
Iuliia A Gracheva, Iuliia V Voitovich, Vladimir I Faerman, Nikolay S Sitnikov, Ekaterina V Myrsikova, Hans-Gunther Schmalz, Elena V Svirshevskaya, Alexey Yu Fedorov
A series of furan-based allocolchicinoids was prepared from commercially available colchicine via a nine-step reaction sequence. Cytostatic activity, cell cycle arrest, apoptosis, tubulin and F-actin expression were studied in vitro in 2D and 3D cultures of normal and tumor epithelial keratinocytes, endothelial and mesenchymal cells. Among the prepared furanoallocolchicine analogues, 14a and 7a displayed the most pronounced anti-cancer activity. These compounds induced two types of effects: (a) cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding (metaphase effect), and (b) pronounced cell stress (as evidenced by the overexpression of tubulin and F-actin), which was caused by the hyperpolarization of mitochondrial and lysosomal membranes (interphase effect)...
November 16, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27912101/the-cytoskeleton-architecture-of-algivorous-protoplast-feeders-viridiraptoridae-rhizaria-indicates-actin-guided-perforation-of-prey-cell-walls
#14
Anna Busch, Sebastian Hess
Several distantly related, phagotrophic microeukaryotes share the remarkable ability to perforate foreign cell walls in a well-defined pattern to acquire protoplast material as food. The underlying cellular processes, especially the local application of cell wall degrading agents, are still unexplored. We examined the distribution of F-actin and alpha-tubulin in the algivorous, viridiraptorid amoeboflagellates Orciraptor agilis and Viridiraptor invadens over their life histories using phalloidin conjugates and immunolocalization...
October 31, 2016: Protist
https://www.readbyqxmd.com/read/27911791/a-functional-role-for-intrinsic-disorder-in-the-tau-tubulin-complex
#15
Ana M Melo, Juliana Coraor, Garrett Alpha-Cobb, Shana Elbaum-Garfinkle, Abhinav Nath, Elizabeth Rhoades
Tau is an intrinsically disordered protein with an important role in maintaining the dynamic instability of neuronal microtubules. Despite intensive study, a detailed understanding of the functional mechanism of tau is lacking. Here, we address this deficiency by using intramolecular single-molecule Förster Resonance Energy Transfer (smFRET) to characterize the conformational ensemble of tau bound to soluble tubulin heterodimers. Tau adopts an open conformation on binding tubulin, in which the long-range contacts between both termini and the microtubule binding region that characterize its compact solution structure are diminished...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911710/eml-proteins-in-microtubule-regulation-and-human-disease
#16
REVIEW
Andrew M Fry, Laura O'Regan, Jessica Montgomery, Rozita Adib, Richard Bayliss
The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27908733/sequences-in-linker-1-domain-of-the-multidrug-resistance-associated-protein-mrp1-or-abcc1-bind-to-tubulin-and-their-binding-is-modulated-by-phosphorylation
#17
Raghuram Ambadipudi, Elias Georges
The multidrug resistant associated protein 1 (or MRP1, ABCC1) encodes two cytoplasmic linker domains (L0 and L1) composed of highly charged sequences with multiple protein kinase A/C phosphorylation sites. In this report we made use of the scanning peptide approach to identify MRP1 linker L1 (L1(MRP1)) interacting proteins. Scanning heptapeptides covering L1(MRP1) 126 amino acids (Ile(846)- Leu(972)) were synthesized and used in pull-down assays to isolate proteins from cell extracts (human multidrug resistant SCLC cell line; H69/AR)...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27906670/stag3-regulates-microtubule-stability-to-maintain-euploidy-during-mouse-oocyte-meiotic-maturation
#18
Mianqun Zhang, Xiaoxin Dai, Yalu Sun, Yajuan Lu, Changyin Zhou, Yilong Miao, Ying Wang, Bo Xiong
Stag3, a meiosis-specific subunit of cohesin complex, has been demonstrated to function in both male and female reproductive systems in mammals. However, its roles during oocyte meiotic maturation have not been fully defined. In the present study, we report that Stag3 uniquely accumulates on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Depletion of Stag3 by gene-targeting morpholino disrupts normal spindle assembly and chromosome alignment in oocytes...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906586/neural-differentiation-of-mesenchymal-stem-cells-on-scaffolds-for-nerve-tissue-engineering-applications
#19
Kerlin Quintiliano, Thayane Crestani, Davi Silveira, Virginia Etges Helfer, Annelise Rosa, Eduardo Balbueno, Daniela Steffens, Geraldo Pereira Jotz, Diogo André Pilger, Patricia Pranke
Scaffolds produced by electrospinning act as supports for cell proliferation and differentiation, improved through the release of neurotrophic factors. The objective of this study was to develop aligned and random nanofiber scaffolds with and without nerve growth factor to evaluate the potential of mesenchymal stem cells (MSCs) for neural differentiation. Nanofiber morphology, diameter, degradability, cell morphology, adhesion, proliferation, viability, cytotoxicity, and neural differentiation were performed to characterize the scaffolds...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27905536/post-translational-incorporation-of-l-phenylalanine-into-the-c-terminus-of-%C3%AE-tubulin-as-a-possible-cause-of-neuronal-dysfunction
#20
Yanina Ditamo, Yanela M Dentesano, Silvia A Purro, Carlos A Arce, C Gastón Bisig
α-Tubulin C-terminus undergoes post-translational, cyclic tyrosination/detyrosination, and L-Phenylalanine (Phe) can be incorporated in place of tyrosine. Using cultured mouse brain-derived cells and an antibody specific to Phe-tubulin, we showed that: (i) Phe incorporation into tubulin is reversible; (ii) such incorporation is not due to de novo synthesis; (iii) the proportion of modified tubulin is significant; (iv) Phe incorporation reduces cell proliferation without affecting cell viability; (v) the rate of neurite retraction declines as level of C-terminal Phe incorporation increases; (vi) this inhibitory effect of Phe on neurite retraction is blocked by the co-presence of tyrosine; (vii) microtubule dynamics is reduced when Phe-tubulin level in cells is high as a result of exogenous Phe addition and returns to normal values when Phe is removed; moreover, microtubule dynamics is also reduced when Phe-tubulin is expressed (plasmid transfection)...
December 1, 2016: Scientific Reports
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