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https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#1
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28212627/genome-wide-identification-of-direct-hbx-genomic-targets
#2
Francesca Guerrieri, Laura Belloni, Daniel D'Andrea, Natalia Pediconi, Loredana Le Pera, Barbara Testoni, Cecilia Scisciani, Oceane Floriot, Fabien Zoulim, Anna Tramontano, Massimo Levrero
BACKGROUND: The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28210225/increased-apoptosis-in-the-paraventricular-nucleus-mediated-by-at1r-ras-erk1-2-signaling-results-in-sympathetic-hyperactivity-and-renovascular-hypertension-in-rats-after-kidney-injury
#3
Hongguo Zhu, Lishan Tan, Yumin Li, Jiawen Li, Minzi Qiu, Lanying Li, Mengbi Zhang, Min Liang, Aiqing Li
Background: The central nervous system plays a vital role in the development of hypertension, but the molecular regulatory mechanisms are not fully understood. This study aimed to explore signaling in the paraventricular nucleus (PVN) which might contribute to renal hypertension. Methods: Renal hypertension model was established by five-sixth nephrectomy operation (5/6Nx) in male Sprague Dawley rats. Ten weeks afterwards, they were random assigned to no treatment, or intracerebroventricular injection (ICV) with artificial cerebrospinal fluid, losartan [angiotensin II receptor type 1 (AT1R) antagonist], farnesylthiosalicylic acid (Ras inhibitor), PD98059 (MEK inhibitor), or SB203580 (p38 inhibitor) and Z-DEVD-FMK (caspase-3 inhibitor)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28207424/skeletal-muscle-wasting-new-role-of-nonclassical-renin-angiotensin-system
#4
Claudio Cabello-Verrugio, Juan C Rivera, Dominga Garcia
PURPOSE OF REVIEW: Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance. RECENT FINDINGS: Recent studies have shown that angiotensin (1-7) [Ang-(1-7)] - a vasoactive peptide of the nonclassical axis in the renin-angiotensin system (RAS) - and its Mas receptor are expressed in skeletal muscle...
February 16, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28204818/reactive-oxygen-species-mediate-angiotensin-ii-induced-transcytosis-of-low-density-lipoprotein-across-endothelial-cells
#5
Fang Bian, Jun Cui, Tao Zheng, Si Jin
The retention of plasma low-density lipoprotein (LDL) particles to subendothelial spaces through transcytosis across the endothelium is the initial step of atherosclerosis (AS). Angiotensin II (Ang II), as the principal effector molecule of the renin-angiotensin system (RAS), is implicated in several important steps of AS development. However, whether or not Ang II can directly exert a pro‑atherogenic effect by promoting LDL transcytosis across endothelial barriers, has not been defined. In the present study, we found that Ang II upregulated intracellular reactive oxygen species (ROS) levels in endothelial cells (ECs) by measuring fluorescence of 2',7'-dichlorofluorescein (DCF‑DA)...
February 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202657/deciphering-the-ras-erk-pathway-in-vivo
#6
REVIEW
Coralie Dorard, Georg Vucak, Manuela Baccarini
The RAS/ERK pathway has been intensely studied for about three decades, not least because of its role in human pathologies. ERK activation is observed in the majority of human cancers; in about one-third of them, it is driven by mutational activation of pathway components. The pathway is arguably one of the best targets for molecule-based pharmacological intervention, and several small-molecule inhibitors are in clinical use. Genetically engineered mouse models have greatly contributed to our understanding of signaling pathways in development, tissue homeostasis, and disease...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28199100/complexes-of-magnetic-nanoparticles-with-cellulose-nanocrystals-as-regenerable-highly-efficient-and-selective-platform-for-protein-separation
#7
Jiaqi Guo, Ilari Filpponen, Leena-Sisko Johansson, Pezhman Mohammadi, Mika Latikka, Markus B Linder, Robin H A Ras, Orlando J Rojas
We present an efficient approach to synthesize cellulose nanocrystal (CNC) hybrids with magnetically responsive Fe3O4 nanoparticles that were synthesized using the (Fe3+/Fe2+) co-precipitation. After TEMPO-catalyzed oxidation of CNC, carbodiimide (EDC/NHS) was used for coupling amine-containing iron oxide nanoparticles that were achieved by dopamine ligand exchange (NH2-Fe3O4 NPs). The as prepared hybrids (Fe3O4@CNC) were further complexed with Cu(II) ions to produce specific protein binding sites. The performance of magnetically responsive Cu-Fe3O4@CNC hybrid was assessed by selectively separating lysozyme from aqueous media...
February 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28197917/sumo-in-drosophila-development
#8
Joseph Cao, Albert J Courey
The ubiquitin -like protein SUMO is conjugated covalently to hundreds of target proteins in organisms throughout the eukaryotic domain. Genetic and biochemical studies using the model organism Drosophila melanogaster are beginning to reveal many essential functions for SUMO in cell biology and development. For example, SUMO regulates multiple signaling pathways such as the Ras/MAPK, Dpp, and JNK pathways. In addition, SUMO regulates transcription through conjugation to many transcriptional regulatory proteins, including Bicoid, Spalt , Scm, and Groucho...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28197625/different-effect-of-resveratrol-to-induction-of-apoptosis-depending-on-the-type-of-human-cancer-cells
#9
Michinori Takashina, Sayaka Inoue, Kei Tomihara, Kengo Tomita, Kohshi Hattori, Qing-Li Zhao, Tokiko Suzuki, Makoto Noguchi, Wakana Ohashi, Yuichi Hattori
The effect of resveratrol on various human cancer cells was investigated with special focus on apoptotic cell death, in an attempt to further characterize its mechanism of action. There were great differences in the anti-viability effect of resveratrol between different types of human cancer cells. While the inhibition of cell viability by resveratrol was marked in U937 and MOLT-4 leukemia cells, resveratrol moderately inhibited cell viability in MCF-7 breast, HepG2 liver, and A549 lung cancer cells, and the effect was slight on cell viability in Caco-2, HCT116, and SW480 colon cancer cells...
January 24, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28196873/lymphotoxin-beta-interacts-with-methylated-egfr-to-mediate-acquired-resistance-to-cetuximab-in-head-and-neck-cancer
#10
Dennis Shin-Shian Hsu, Wei-Lun Hwang, Chiou-Hwa Yuh, Chen-Hsi Chu, Yang-Hui Ho, Pon-Bo Chen, Han-Syuan Lin, Hua-Kuo Lin, Shih-Pei Wu, Chih-Yi Lin, Wen-Hao Hsu, Hsin-Yi Lan, Hsiao-Jung Wang, Shyh-Kuan Tai, Mien-Chie Hung, Muh-Hwa Yang
PURPOSE: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation-mediated de novo resistance. Here we investigated the driver gene mutation-independent mechanism for cetuximab resistance in HNSCC. EXPERIMENTAL DESIGN: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28196746/rap1gap-inhibits-tumor-progression-in-endometrial-cancer
#11
Masato Tamate, Ryoichi Tanaka, Hiroyuki Osogami, Motoki Matsuura, Seiro Satohisa, Masahiro Iwasaki, Tsuyoshi Saito
OBJECTIVE: Endometrioid adenocarcinoma (EAC) is a common endometrial cancer with recent dramatic increases in incidence. Previous findings indicate that Rap1GAP acts as a tumor suppressor inhibiting Ras superfamily protein Rap1 in multiple aggressive carcinomas; however, Rap1GAP expression in EAC has not been investigated. In this study, the tumor suppressing activity of Rap1GAP in EAC was explored. METHODS: EAC cell lines were used to examine Rap1GAP levels by real-time RT-PCR and western blotting and the effects of Rap1GAP on cancer cell invasion and migration...
February 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28194147/freshwater-recirculating-aquaculture-system-operations-drive-biofilter-bacterial-community-shifts-around-a-stable-nitrifying-consortium-of-ammonia-oxidizing-archaea-and-comammox-nitrospira
#12
Ryan P Bartelme, Sandra L McLellan, Ryan J Newton
Recirculating aquaculture systems (RAS) are unique engineered ecosystems that minimize environmental perturbation by reducing nutrient pollution discharge. RAS typically employ a biofilter to control ammonia levels produced as a byproduct of fish protein catabolism. Nitrosomonas (ammonia-oxidizing), Nitrospira, and Nitrobacter (nitrite-oxidizing) species are thought to be the primary nitrifiers present in RAS biofilters. We explored this assertion by characterizing the biofilter bacterial and archaeal community of a commercial scale freshwater RAS that has been in operation for >15 years...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28193718/h-ras-isoform-mediates-protection-against-pressure-overload-induced-cardiac-dysfunction-in-part-through-activation-of-akt
#13
Takahisa Matsuda, Jae Im Jeong, Shohei Ikeda, Takanobu Yamamoto, Shumin Gao, Gopal J Babu, Peiyong Zhai, Dominic P Del Re
BACKGROUND: In general, Ras proteins are thought to promote cardiac hypertrophy, an important risk factor for cardiovascular disease and heart failure. However, the contribution of different Ras isoforms has not been investigated. The objective of this study was to define the role of H- and K-Ras in modulating stress-induced myocardial hypertrophy and failure. METHODS AND RESULTS: We used H- and K-Ras gene knockout mice and subjected them to pressure overload to induce cardiac hypertrophy and dysfunction...
February 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28192409/melanocyte-transformation-requires-complete-loss-of-all-pocket-protein-function-via-a-mechanism-that-mitigates-the-need-for-mapk-pathway-activation
#14
I D Tonks, P Mukhopadhyay, W A Schroder, A Sorolla, A W Mould, H Y Handoko, B Ferguson, H K Muller, P Keith, N K Hayward, G J Walker, G F Kay
Deregulation of p16INK4A is a critical event in melanoma susceptibility and progression. It is generally assumed that the major effect of loss of p16 function is mediated through the CDK-cyclin pathway via its influence on the pocket protein (PP) pRb. However, there are also two other PPs, p107 and p130, which, when phosphorylated by CDK-cyclin complexes, play a role in permitting cell progression. Cohorts of mice carrying melanocyte-specific knockouts (KOs) of various combinations of the three PPs were generated...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28188843/rapid-expression-of-rasd1-is-regulated-by-estrogen-receptor-dependent-intracellular-signaling-pathway-in-the-mouse-uterus
#15
Hye-Ryun Kim, Kil-Sang Cho, Eunhye Kim, Ok-Hee Lee, Hyemin Yoon, Sangho Lee, Sohyeon Moon, Miseon Park, Kwonho Hong, Younghwa Na, Ji-Eun Shin, Hwang Kwon, Haengseok Song, Dong Hee Choi, Youngsok Choi
Dexamethasone-induced RAS-related protein 1 (RASD1) is a signaling protein that is involved in various cellular processes. In a previous study, we found that RASD1 expression was down-regulated in the uterine endometrium of repeated implantation failure patients. The study aim was to determine whether RASD1 is expressed in the endometrium of mouse uterus and how it is regulated by steroid hormones during the estrous cycle. In this study, we investigated RASD1 expression and regulation in an ovariectomized female mouse model...
February 7, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28188432/correlations-of-igf-1r-and-cox-2-expressions-with-ras-and-braf-genetic-mutations-clinicopathological-features-and-prognosis-of-colorectal-cancer-patients
#16
Mei Jin, Zi-Wen Long, Jing Yang, Xiang Lin
This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry...
February 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28188228/time-resolved-phosphoproteome-analysis-of-paradoxical-raf-activation-reveals-novel-targets-of-erk
#17
Peter Kubiniok, Hugo Lavoie, Marc Therrien, Pierre Thibault
Small molecules targeting aberrant RAF activity, like Vemurafenib (PLX4032), are highly effective against cancers harboring the V600E BRAF mutation, and are now approved for clinical use against metastatic melanoma. However, in tissues showing elevated RAS activity and in RAS-mutant tumors, these inhibitors stimulate RAF dimerization, resulting in inhibitor resistance and downstream paradoxical ERK activation. To understand the global signaling response of cancer cells to RAF inhibitors, we profiled the temporal changes of the phosphoproteome of two colon cancer cell lines (Colo205 and HCT116) that respond differently to Vemurafenib...
February 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28187408/analysis-of-differential-gene-expression-by-rna-seq-data-in-brain-areas-of-laboratory-animals
#18
Vladimir N Babenko, Anatoly O Bragin, Anastasia M Spitsina, Irina V Chadaeva, Elvira R Galieva, Galina V Orlova, Irina V Medvedeva, Yuriy L Orlov
Computer analysis of gene expression in the nervous system plays a fundamental role in biology, genetics, and neurosciences. We studied molecular and genetic mechanisms of enhanced aggressiveness in comparison with tolerant behaviour using experimental animal models developed at the Institute of Cytology and Genetics SB RAS. Grey rats (Rattus norvegicus) have been subjected to selection during several generations in two directions – friendly, tolerant behaviour towards man (tame grey rats) and increased aggressive behaviour...
December 18, 2016: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28185929/chitosan-oligosaccharide-inhibits-egf-induced-cell-growth-possibly-through-blockade-of-epidermal-growth-factor-receptor-mitogen-activated-protein-kinase-pathway
#19
Qingsong Xu, Wenjing Wang, Wen Yang, Yuguang Du, Linsheng Song
Chitosan oligosaccharide (COS) has been shown to regulate various cellular and biological functions. Epidermal growth factor (EGF) plays a significant role in tumorigenesis and invasiveness of some cancers. The aim of this study was to evaluate the effects of COS on EGF-induced cell growth and the further mechanisms. The results demonstrated that COS could inhibit EGF-induced epithelial GE11 cells proliferation in a dose dependent manner. In addition, EGF stimulated the epithelial cells to undergo morphological alteration, exhibiting mesenchymal cells higher metastatic and invasive potential, however, COS could partly suppress aforementioned morphological change...
February 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28184004/ets-proto-oncogene-1-transcriptionally-up-regulates-the-cholangiocyte-senescence-associated-protein-cyclin-dependent-kinase-inhibitor-2a
#20
Steven P O'Hara, Patrick L Splinter, Christy E Trussoni, Maria J Lorenzo Pisarello, Lorena Loarca, Noah S Splinter, Bryce F Schutte, Nicholas F LaRusso
Primary sclerosing cholangitis (PSC) is a chronic, fibro-inflammatory cholangiopathy (disease of the bile ducts) of unknown pathogenesis. We reported that cholangiocyte senescence features prominently in PSC and neuroblastoma RAS viral oncogene homolog (NRAS) is activated in PSC cholangiocytes. Additionally, persistent microbial insult (e.g., lipopolysaccharides [LPS]) induces Cyclin Dependent Kinase Inhibitor 2A (CDKN2A/p16INK4a) expression and senescence in cultured cholangiocytes in an NRAS-dependent manner...
February 8, 2017: Journal of Biological Chemistry
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