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https://www.readbyqxmd.com/read/29764864/targeting-the-hsp40-hsp70-chaperone-axis-as-a-novel-strategy-to-treat-castration-resistant-prostate-cancer
#1
Michael A Moses, Yeong Sang Kim, Genesis M Rivera-Marquez, Nobu Oshima, Matthew J Watson, Kristin Beebe, Catherine Wells, Sunmin Lee, Abbey D Zuehlke, Hao Shao, William E Bingman, Vineet Kumar, Sanjay Malhotra, Nancy L Weigel, Jason E Gestwicki, Jane Trepel, Leonard M Neckers
Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with heat shock protein 40 (Hsp40)...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764463/lncmapk6-drives-mapk6-expression-and-liver-tic-self-renewal
#2
Guanqun Huang, Hui Jiang, Yueming He, Ye Lin, Wuzheng Xia, Yuanwei Luo, Min Liang, Boyun Shi, Xinke Zhou, Zhixiang Jian
BACKGROUND: Liver tumor initiating cells (TICs) have self-renewal and differentiate capacities, and largely contribute to tumor initiation, metastasis and drug resistance. MAPK signaling is a critical pathway in many biological processes, while its role in liver TICs hasn't been explored. METHODS: Online-available dataset was used for unbiased screening. Liver TICs were examined CD133 FACS or oncosphere formation. TIC self-renewal was detected by oncosphere formation and tumor initiation assay...
May 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29758198/the-lncrna-tug1-mir-145-5p-fgf10-regulates-proliferation-and-migration-in-vsmcs-of-hypertension
#3
Lin Shi, Caijun Tian, Lingzhi Sun, Feifei Cao, Zhaoyang Meng
Vascular remodeling is a characteristic pathological feature of hypertension, it can cause of increasing vascular resistance and decrease of compliance. Vascular smooth muscle cell (VSMCs) dysfunction is the important foundation of vascular remodeling. Increasing evidences have revealed that lncRNA is an important regulatory factor of VSMC function. In this paper, we explored the function of lncRNA TUG1 in vascular remodeling of hypertension. Here, we found that lncRNA TUG1 was highly expressed in aorta of spontaneously hypertensive rats (SHR) rats and promoted the proliferation and migration of VSMCs (SHR-VSMCs)...
May 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29757292/desthiobiotin-streptavidin-affinity-mediated-purification-of-rna-interacting-proteins-in-mesothelioma-cells
#4
Jelena Kresoja-Rakic, Emanuela Felley-Bosco
The in vitro RNA-pulldown is still largely used in the first steps of protocols aimed at identifying RNA-binding proteins that recognize specific RNA structures and motifs. In this RNA-pulldown protocol, commercially synthesized RNA probes are labeled with a modified form of biotin, desthiobiotin, at the 3' terminus of the RNA strand, which reversibly binds to streptavidin and thus allows elution of proteins under more physiological conditions. The RNA-desthiobiotin is immobilized through interaction with streptavidin on magnetic beads, which are used to pull down proteins that specifically interact with the RNA of interest...
April 25, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29753769/fish-samhd1-performs-as-an-activator-for-ifn-expression
#5
Meifeng Li, Xiaowen Xu, Zeyin Jiang, Changxin Liu, Xiao Shi, Guoqin Qi, Yinping Li, Xin Chen, Qingli Huang, Huiling Mao, Chengyu Hu
As a host limiting factor, Sterile Alpha Motif and Histidine-Aspartate Domain 1 protein (SAMHD1) is associated with IRF3-mediated antiviral and apoptotic responses in mammals. However, the antiviral mechanism of SAMHD1 remains indistinct in fish. In this study, we found the expression of Ctenopharyngodon idella SAMHD1 (MF326081) was up-regulated after transfection with poly I:C (dsRNA analog), B-DNA or Z-DNA into C. idella kidney cells (CIKs), but these expression profiles had no obvious change when the cells were incubated with these nucleic acids...
May 10, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29752407/integrin-%C3%AE-v%C3%AE-3-associated-daam1-is-essential-for-collagen-induced-invadopodia-extension-and-cell-haptotaxis-in-breast-cancer-cells
#6
Ting Yan, Ailiang Zhang, Fangfang Shi, Fei Chang, Jie Mei, Yongjian Liu, Yichao Zhu
The formin protein dishevelled-associated activator of morphogenesis 1 (DAAM1) polymerizes straight actin filaments and mediates migration of cancer cells. However, how DAAM1 governs cell haptotaxis in response to collagen remains unexplored in breast cancer cells. We hypothesized that DAAM1 mediates invadopodia extension and cell haptotaxis in response to type IV collagen in association with integrin receptors. Using Boyden chamber membranes coated with type IV collagen, we show here that type IV collagen activates both DAAM1 and  Ras homolog family member A (RHOA)  and promotes haptotaxis of MDA-MB-231 and MDA-MB-453 breast cancer cells, a process abolished by treatment with the integrin αvβ3 inhibitor cyclo(-RGDfK)...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29744291/poly-rc-binding-protein-2-pcbp2-promotes-the-viability-of-human-gastric-cancer-cells-by-regulating-cdk2
#7
Changyu Chen, Jun Lei, Qiang Zheng, Sheng Tan, Keshuo Ding, Changjun Yu
Survival rates for patients with gastric cancer, especially the advanced form, remain poor and the development of targeted treatments is hampered by a lack of efficient biological targets. Poly(rC) binding protein 2 (PCBP2) is an RNA-binding protein that contributes to mRNA stabilization, translational silencing and enhancement and it has been implicated as a promoter of gastric cancer growth. In the present study, we demonstrated that the expression level of PCBP2 was higher in human gastric cancer tissues compared to adjacent normal gastric tissues...
May 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29743600/trafficking-localization-and-degradation-of-the-na-hco-3-co-transporter-nbcn1-in-kidney-and-breast-epithelial-cells
#8
Christina Wilkens Olesen, Jens Vogensen, Ida Axholm, Marc Severin, Julie Schnipper, Isabella Skandorff Pedersen, Jakob Hjorth von Stemann, Jacob Morville Schrøder, Dan Ploug Christensen, Stine Falsig Pedersen
The Na+;HCO3- co-transporter NBCn1 (SLC4A7) is a major regulator of intracellular pH yet its trafficking and turnover are essentially unstudied. Here, we used MDCK-II and MCF-7 cells to investigate these processes in epithelial cells. GFP-NBCn1 membrane localization was abolished by truncation of the full NBCn1 C-terminal tail (C-tail) yet did not require the C-terminal PDZ-binding motif (ETSL). Glutathione-S-Transferase-pulldown of the C-tail followed by mass spectrometry analysis revealed putative interactions with multiple sorting-, degradation- and retention factors, including the scaffolding protein RACK1...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29724821/phosphoinositide-interacting-regulator-of-trp-pirt-has-opposing-effects-on-human-and-mouse-trpm8-ion-channels
#9
Jacob K Hilton, Taraneh Salehpour, Nicholas J Sisco, Parthasarathi Rath, Wade D Van Horn
Transient receptor potential melastatin 8 (TRPM8) is a cold-sensitive ion channel with diverse physiological roles. TRPM8 activity is modulated by many mechanisms, including an interaction with the small membrane protein phosphoinositide-interacting regulator of TRP (PIRT). Here, using comparative electrophysiology experiments, we identified species-dependent differences between the human and mouse TRPM8-PIRT complexes. We found that human PIRT attenuated human TPRM8 conductance, unlike mouse PIRT, which enhanced mouse TRPM8 conductance...
May 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29724197/the-role-of-vimentin-in-the-tumor-marker-nup88-dependent-multinucleated-phenotype
#10
Masaki Makise, Hideaki Nakamura, Akihiko Kuniyasu
BACKGROUND: Nucleoporin Nup88, a component of nuclear pore complexes, is known to be overexpressed in several types of tumor tissue. The overexpression of Nup88 has been reported to promote the early step of tumorigenesis by inducing multinuclei in both HeLa cells and a mouse model. However, the molecular basis of how Nup88 leads to a multinucleated phenotype remains unclear because of a lack of information concerning its binding partners. In this study, we characterize a novel interaction between Nup88 and vimentin...
May 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29722252/creatine-monohydrate-supplementation-during-eight-weeks-of-progressive-resistance-training-increases-strength-in-as-little-as-two-weeks-without-reducing-markers-of-muscle-damage
#11
Mojtaba Kaviani, Aboozar Abassi, Philip D Chilibeck
BACKGROUND: Creatine supplementation (Cr) increases strength during resistance training, but the time course of this strength increase is unclear. The aim was to determine the precise time course by which Cr could increase strength and whether Cr prevents muscle damage during eight weeks of resistance training. METHODS: Young males were randomized (double blind) to Cr (n=9, 0.07g/kg/d) and placebo (n=9) during 8-weeks of resistance training (3d/week). Strength was assessed across six exercises every two weeks...
May 2, 2018: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/29720973/a-deubiquitinating-enzyme-ubp14-is-required-for-development-stress-response-nutrient-utilization-and-pathogenesis-of-magnaporthe-oryzae
#12
Zhao Wang, Hong Zhang, Caiyun Liu, Junjie Xing, Xiao-Lin Chen
Ubiquitination is an essential protein modification in eukaryotic cells, which is reversible. Deubiquitinating enzymes (DUBs) catalyze deubiquitination process to reverse ubiquitination, maintain ubiquitin homeostasis or promote protein degradation by recycling ubiquitins. In order to investigate effects of deubiquitination process in plant pathogenic fungus Magnaporthe oryzae , we generated deletion mutants of MoUBP14 . Ortholog of MoUbp14 was reported to play general roles in ubiquitin-mediated protein degradation in Saccharomyces cerevisiae ...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29700467/digestion-ligation-only-hi-c-is-an-efficient-and-cost-effective-method-for-chromosome-conformation-capture
#13
Da Lin, Ping Hong, Siheng Zhang, Weize Xu, Muhammad Jamal, Keji Yan, Yingying Lei, Liang Li, Yijun Ruan, Zhen F Fu, Guoliang Li, Gang Cao
Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments...
April 26, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29644259/rna-cap-methyltransferase-activity-assay
#14
Jackson B Trotman, Daniel R Schoenberg
Methyltransferases that methylate the guanine-N7 position of the mRNA 5' cap structure are ubiquitous among eukaryotes and commonly encoded by viruses. Here we provide a detailed protocol for the biochemical analysis of RNA cap methyltransferase activity of biological samples. This assay involves incubation of cap-methyltransferase-containing samples with a [32 P]G-capped RNA substrate and S-adenosylmethionine (SAM) to produce RNAs with N7-methylated caps. The extent of cap methylation is then determined by P1 nuclease digestion, thin-layer chromatography (TLC), and phosphorimaging...
March 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29595414/the-flag-regulator-is-involved-in-length-control-of-the-polar-flagella-of-campylobacter-jejuni
#15
Tomoharu Inoue, Clive S Barker, Hideyuki Matsunami, Shin-Ichi Aizawa, Fadel A Samatey
Campylobacter jejuni cells have bipolar flagella. Both flagella have similar lengths of about one helical turn, or 3.53±0.52 µm. The flagellar filament is composed of two homologous flagellins: FlaA and FlaB. Mutant strains that express either FlaA or FlaB alone produce filaments that are shorter than those of the wild-type. It is reported that the flaG gene could affect filament length in some species of bacteria, but its function remains unknown. We introduced a flaG-deletion mutation into the C. jejuni wild-type strain and flaA- or flaB-deletion mutant strains, and observed their flagella by microscopy...
March 29, 2018: Microbiology
https://www.readbyqxmd.com/read/29577871/long-noncoding-rna-malat1-regulates-generation-of-reactive-oxygen-species-and-the-insulin-responses-in-male-mice
#16
Jingshu Chen, Sui Ke, Lei Zhong, Jing Wu, Alexander Tseng, Benjamin Morpurgo, Andrei Golovko, Gang Wang, James J Cai, Xi Ma, Defa Li, Yanan Tian
The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA and its overexpression is associated with the development of many types of malignancy. MALAT1 null mice show no overt phenotype. However, in transcriptome analysis of MALAT1 null mice we found significant upregulation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulated antioxidant genes including Nqo1 and Cat with significant reduction in reactive oxygen species (ROS) and greatly reduced ROS-generated protein carbonylation in hepatocyte and islets...
March 22, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29567837/the-brd3-et-domain-recognizes-a-short-peptide-motif-through-a-mechanism-that-is-conserved-across-chromatin-remodelers-and-transcriptional-regulators
#17
Dorothy C Wai, Taylor N Szyszka, Amy E Campbell, Cherry Kwong, Lorna E Wilkinson-White, Ana P G Silva, Jason K K Low, Ann H Kwan, Roland Gamsjaeger, James N Chalmers, Wayne M Patrick, Bin Lu, Christopher R Vakoc, Gerd A Blobel, Joel P Mackay
Members of the bromodomain and extra-terminal domain (BET) family of proteins (bromodomain-containing (BRD) 2, 3, 4 and T) are widely expressed and highly conserved regulators of gene expression in eukaryotes. These proteins have been intimately linked to human disease and more than a dozen clinical trials are currently underway to test BET-protein inhibitors as modulators of cancer therapies. However, although it is clear that these proteins use their bromodomains to bind both histones and transcription factors bearing acetylated lysine residues, the molecular mechanisms by which BET-family proteins regulate gene expression are not well defined...
March 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29549126/the-major-facilitator-transporter-str3-is-required-for-low-affinity-heme-acquisition-in-schizosaccharomyces-pombe
#18
Vincent Normant, Thierry Mourer, Simon Labbe
In the fission yeast Schizosaccharomyces pombe , acquisition of exogenous heme is largely mediated by the cell membrane-associated Shu1. Here, we report that Str3, a member of the major facilitator superfamily of transporters promotes cellular heme import. Using a strain that cannot synthesize heme de novo ( hem1Δ ) and lacks Shu1, we found that the heme-dependent growth deficit of this strain is rescued by hemin supplementation in the presence of Str3. Microscopic analyses of a hem1Δ shu1Δ str3Δ mutant strain in the presence of the heme analog zinc mesoporphyrin IX (ZnMP) revealed that ZnMP fails to accumulate within the mutant cells...
March 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29540601/positive-regulation-of-hepatitis-e-virus-replication-by-microrna-122
#19
Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
Molecular mechanisms of liver pathology and clinical disease in HEV infection remain unclear. MicroRNAs are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using genotype 1, 2, 3 and 4 HEV sequences showed that majority of genomes (203/222) harbor at least one miR-122/miR-122* target site...
March 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29540185/linc00210-drives-wnt-%C3%AE-catenin-signaling-activation-and-liver-tumor-progression-through-ctnnbip1-dependent-manner
#20
Xiaomin Fu, Xiaoyan Zhu, Fujun Qin, Yong Zhang, Jizhen Lin, Yuechao Ding, Zihe Yang, Yiman Shang, Li Wang, Qinxian Zhang, Quanli Gao
BACKGROUND: Liver tumor initiating cells (TICs) have self-renewal and differentiation properties, accounting for tumor initiation, metastasis and drug resistance. Long noncoding RNAs are involved in many physiological and pathological processes, including tumorigenesis. DNA copy number alterations (CNA) participate in tumor formation and progression, while the CNA of lncRNAs and their roles are largely unknown. METHODS: LncRNA CNA was determined by microarray analyses, realtime PCR and DNA FISH...
March 14, 2018: Molecular Cancer
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