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Ras protein

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https://www.readbyqxmd.com/read/28929213/to-finish-things-well-cysteine-methylation-ensures-selective-gtpase-membrane-localization-and-signalling
#1
REVIEW
José Cansado
Isoprenylcysteine-O-Carboxyl Methyltransferase (ICMT) catalyzes the final step in the prenylation process of different proteins including members of the Ras superfamily of GTPases. While cysteine methylation is essential in mammalian cells for growth, membrane association, and signalling by Ras and Rho GTPases, its role during signal transduction events in simple eukaryotes like yeasts appears irrelevant. By using a multidisciplinary approach our group has recently shown that, contrary to this initial assumption, in the fission yeast Schizosaccharomyces pombe ICMT activity encoded by the Mam4 gene is not only important to promote selective plasma membrane targeting of Ras and specific Rho GTPases, but also to allow precise downstream signalling to the mitogen-activated protein kinase and target of rapamycin pathways in response to diverse environmental cues...
September 19, 2017: Current Genetics
https://www.readbyqxmd.com/read/28929017/calcitonin-receptor-expression-in-medullary-thyroid-carcinoma
#2
Virginia Cappagli, Catarina Soares Potes, Luciana Bueno Ferreira, Catarina Tavares, Catarina Eloy, Rossella Elisei, Manuel Sobrinho-Simões, Peter J Wookey, Paula Soares
BACKGROUND: Calcitonin expression is a well-established marker for medullary thyroid carcinoma (MTC); yet the role of calcitonin receptor (CTR), its seven-transmembrane G-protein coupled receptor, remains to be established in C-cells derived thyroid tumors. The aim of this work was to investigate CTR expression in MTC and to correlate such expression with clinicopathological features in order to evaluate its possible role as a prognostic indicator of disease aggressiveness and outcome...
2017: PeerJ
https://www.readbyqxmd.com/read/28928410/ang-1-7-is-an-endogenous-%C3%AE-arrestin-biased-agonist-of-the-at1-receptor-with-protective-action-in-cardiac-hypertrophy
#3
Larissa B Teixeira, Lucas T Parreiras-E-Silva, Thiago Bruder-Nascimento, Diego A Duarte, Sarah C Simões, Rafael M Costa, Deisy Y Rodríguez, Pedro A B Ferreira, Carlos A A Silva, Emiliana P Abrao, Eduardo B Oliveira, Michel Bouvier, Rita C Tostes, Claudio M Costa-Neto
The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor and known to counterbalance many of the deleterious effects of AngII. AT1R signaling triggered by β-arrestin-biased agonists has been associated to cardioprotection. Because position 8 in AngII is important for G protein activation, we hypothesized that Ang-(1-7) could be an endogenous β-arrestin-biased agonist of the AT1R...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927155/ras-protein-activator-like-1-is-functionally-involved-in-hypoxia-resistance-in-breast-cancer-cells-by-targeting-hypoxia-inducible-factor-1%C3%AE
#4
Ziming Huang, Rong Wang, Gang Wei, Ran Jiang, Yuan Zheng, Yiwen Tian, Bo Chen, Chunmei Ye, Mingxing Xue, Chunjiao Yu
RAS protein activator-like 1 (RASAL1) is a member of the RAS GTPase-activating protein family, and previous studies indicate that RASAL1 is involved in the progression of hypoxia resistance in breast cancer cells. In the present study, increased levels of hypoxia inducible factor-1α (HIF-1α) were observed to be accompanied with increased expression of RASAL1 in the breast cancer cell lines MCF-7 and MDA-MB-231 cells under hypoxia. Based on this, it was postulated that RASAL1 may serve a functional role in the development of hypoxia resistant in breast cancer cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927034/cyclin-d3-deficiency-inhibits-skin-tumor-development-but-does-not-affect-normal-keratinocyte-proliferation
#5
Sung Hyun Lee, Xian Wang, Sun Hye Kim, Yongbaek Kim, Marcelo L Rodriguez-Puebla
Rearrangement and amplification of the D-type cyclin genes have been reported in human cancer. Previous studies have demonstrated that Ras-mediated skin tumorigenesis depends on pathways that act through cyclin D1 and D2; however, the role of cyclin D3 remains unknown. The present study demonstrates that cyclin D3 ablation does not affect keratinocyte proliferation, but instead increases apoptosis levels in the bulge region of the hair follicle. Consequently, cyclin D3 ablation reduces skin papilloma development in a Ras-dependent carcinogenesis model...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925496/study-on-the-relationship-between-the-rassf10-gene-and-the-biological-behavior-of-hepatocellular-carcinoma-cells
#6
J Xie, Y Chen, F Meng, T Shu, Y Liu, L Zhang, Z-X Zhang
OBJECTIVE: To investigate the relationship between Ras association domain family gene 10 (RASSF10 gene) and the biological behavior of hepatocellular carcinoma (HCC), including proliferation, invasion, and metastasis. MATERIALS AND METHODS: HCC cell lines were generated with stable overexpression or low expression of RASSF10 protein. A cell line transfected with an empty vector was treated as control. At 12, 24, 48, and 72 h, the cell proliferation was determined by MTT assay, the invasion ability was determined by Transwell chambers, and the scratch assay was used to assess the migration ability...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28922368/a-tree-of-life-based-on-ninety-eight-expressed-genes-conserved-across-diverse-eukaryotic-species
#7
Pawan Kumar Jayaswal, Vivek Dogra, Asheesh Shanker, Tilak Raj Sharma, Nagendra Kumar Singh
Rapid advances in DNA sequencing technologies have resulted in the accumulation of large data sets in the public domain, facilitating comparative studies to provide novel insights into the evolution of life. Phylogenetic studies across the eukaryotic taxa have been reported but on the basis of a limited number of genes. Here we present a genome-wide analysis across different plant, fungal, protist, and animal species, with reference to the 36,002 expressed genes of the rice genome. Our analysis revealed 9831 genes unique to rice and 98 genes conserved across all 49 eukaryotic species analysed...
2017: PloS One
https://www.readbyqxmd.com/read/28919784/durable-complete-remission-of-poor-performance-status-metastatic-lung-adenocarcinoma-patient-treated-with-second-line-erlotinib-a-case-report
#8
Dragana Jovanovic, Ruza Stevic, Marta Velinovic, Milica Kontic, Dragana Maric, Jelena Spasic, Davorin Radosavljevic
This paper presents a rare case of an elderly patient treated with erlotinib for disseminated lung adenocarcinoma with poor performance status (Eastern Cooperative Oncology Group performance status [PS]3). This treatment led to a long duration of complete remission according to Response Evaluation Criteria in Solid Tumors 1.1 - almost 7 years (81 months) of progression-free survival (PFS) and overall survival (OS) of 10 years by March 2017. The treatment with erlotinib started in September 2008 and it was well tolerated with no adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919108/the-renin-angiotensin-system-regulates-neurodegeneration-in-a-mouse-model-of-optic-neuritis
#9
Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Chikako Harada, Takayuki Harada
The major role of the renin-angiotensin system (RAS), including that of angiotensin II (Ang II), the principal effector molecule, in the cardiovascular system is well known. Increasing evidence suggests that the RAS also plays a role in the development of autoimmune diseases. Optic neuritis (ie, inflammation of the optic nerve, with retinal ganglion cell [RGC] loss) is strongly associated with multiple sclerosis (MS). Herein, we investigated the effects of candesartan, an Ang II receptor antagonist, on optic neuritis in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
September 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28918901/mtor-inhibition-restores-amino-acid-balance-in-cells-dependent-on-catabolism-of-extracellular-protein
#10
Michel Nofal, Kevin Zhang, Seunghun Han, Joshua D Rabinowitz
Scavenging of extracellular protein via macropinocytosis is an alternative to monomeric amino acid uptake. In pancreatic cancer, macropinocytosis is driven by oncogenic Ras signaling and contributes substantially to amino acid supply. While Ras signaling promotes scavenging, mTOR signaling suppresses it. Here, we present an integrated experimental-computational method that enables quantitative comparison of protein scavenging rates across cell lines and conditions. Using it, we find that, independently of mTORC1, amino acid scarcity induces protein scavenging and that under such conditions the impact of mTOR signaling on protein scavenging rate is minimal...
September 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28917843/rapgef2-a-guanine-nucleotide-exchange-factor-for-rap1-small-gtpases-plays-a-crucial-role-in-adherence-junction-aj-formation-in-radial-glial-cells-through-erk-mediated-upregulation-of-the-aj-constituent-protein-expression
#11
Maged Ibrahim Farag, Yoko Yoshikawa, Kazuhiro Maeta, Tohru Kataoka
Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap1, characterized by possession of the Ras/Rap-associating domains and implicated in the etiology of schizophrenia. We previously found that dorsal telencephalon-specific Rapgef2 conditional knockout mice exhibits severe defects in formation of apical surface adherence junctions (AJs) and localization of radial glial cells (RGCs). In this study, we analyze the underlying molecular mechanism by using primary cultures of RGCs established from the developing cerebral cortex...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28916945/simvastatin-enhances-radiation-sensitivity-of-colorectal-cancer-cells
#12
Georgios Karagkounis, Jennifer DeVecchio, Sylvain Ferrandon, Matthew F Kalady
INTRODUCTION: Neoadjuvant chemoradiation (CRT) for rectal cancer induces variable responses, and better response has been associated with improved oncologic outcomes. Our group has previously shown that the administration of HMG-CoA reductase inhibitors, commonly known as statins, is associated with improved response to neoadjuvant CRT in rectal cancer patients. The purpose of this study was to study the effects of simvastatin on colorectal cancer cells and explore its potential as a radiation-sensitizer in vitro...
September 15, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28915601/mir-148a-impairs-ras-erk-signaling-in-b-lymphocytes-by-targeting-sos-proteins
#13
Julia Alles, Nicole Ludwig, Stefanie Rheinheimer, Petra Leidinger, Friedrich A Grässer, Andreas Keller, Eckart Meese
Although microRNAs have been recognized as central cellular regulators, there is an evident lack of knowledge about their targets. Here, we analyzed potential target genes for miR-148a functioning in Ras signaling in B cells, including SOS1 and SOS2. A dual-luciferase reporter assay showed significantly decreased luciferase activity upon ectopic overexpression of miR-148a in HEK-293T cells that were co-transfected with the 3'UTR of either SOS1 or SOS2. Each of the 3'UTRs of SOS1 and SOS2 contained two binding sites for miR-148a both of which were necessary for the decreased luciferase activity...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915321/regulation-and-functions-of-the-renin-angiotensin-system-in-white-and-brown-adipose-tissue
#14
Mandana Pahlavani, Nishan S Kalupahana, Latha Ramalingam, Naima Moustaid-Moussa
The renin angiotensin system (RAS) is a major regulator of blood pressure, fluid, and electrolyte homeostasis. RAS precursor angiotensinogen (Agt) is cleaved into angiotensin I (Ang I) and II (Ang II) by renin and angiotensin converting enzyme (ACE), respectively. Major effects of Ang II, the main bioactive peptide of this system, is mediated by G protein coupled receptors, Angiotensin Type 1 (AGTR1, AT1R) and Type 2 (AGTR2, AT2R) receptors. Further, the discovery of additional RAS peptides such as Ang 1-7 generated by the action of another enzyme ACE2 identified novel functions of this complex system...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28912723/increased-hemodynamic-load-in-early-embryonic-stages-alters-myofibril-and-mitochondrial-organization-in-the-myocardium
#15
Madeline Midgett, Claudia S López, Larry David, Alina Maloyan, Sandra Rugonyi
Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease (CHD). However, the detrimental remodeling processes that relate altered blood flow to cardiac malformation and defects remain unclear. Heart development is a finely orchestrated process with rapid transformations that occur at the tissue, cell, and subcellular levels. Myocardial cells play an essential role in cardiac tissue maturation by aligning in the direction of stretch and increasing the number of contractile units as hemodynamic load increases throughout development...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28912101/importance-of-the-rem-ras-exchange-domain-for-membrane-interactions-by-rasgrp3
#16
Agnes Czikora, Noemi Kedei, Heather Kalish, Peter M Blumberg
RasGRP comprises a family of guanine nucleotide exchange factors, regulating the dissociation of GDP from Ras GTPases to enhance the formation of the active GTP-bound form. RasGRP1 possesses REM (Ras exchange), GEF (catalytic), EF-hand, C1, SuPT (suppressor of PT), and PT (plasma membrane-targeting) domains, among which the C1 domain drives membrane localization in response to diacylglycerol or phorbol ester and the PT domain recognizes phosphoinositides. The homologous family member RasGRP3 shows less plasma membrane localization...
September 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28911610/myrciaria-cauliflora-extract-improves-diabetic-nephropathy-via-suppression-of-oxidative-stress-and-inflammation-in-streptozotocin-nicotinamide-mice
#17
Jeng-Dong Hsu, Chia-Chun Wu, Chi-Nan Hung, Chau-Jong Wang, Hui-Pei Huang
Myrciaria cauliflora is a functional food rich in anthocyanins, possessing antioxidative and anti-inflammatory properties. Our previous results demonstrated M. cauliflora extract (MCE) had beneficial effects in diabetic nephropathy (DN) and via the inhibition of Ras/PI3K/Akt and kidney fibrosis-related proteins. The purpose of this study was to assess the benefit of MCE in diabetes associated with kidney inflammation and glycemic regulation in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Compared with the untreated diabetic group, MCE significantly improved blood glucose and serum biochemical characteristic levels...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904816/regulation-of-hnrnpa1-by-micrornas-controls-the-mir-18a-k-ras-axis-in-chemotherapy-resistant-ovarian-cancer
#18
Cristian Rodriguez-Aguayo, Paloma Del C Monroig, Roxana S Redis, Emine Bayraktar, Maria I Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K Sood, George A Calin, Gabriel Lopez-Berestein
The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the K-RAS oncogene...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28903430/resveratrol-inhibits-age-dependent-spontaneous-tumorigenesis-by-sirt1-mediated-post-translational-modulations-in-the-annual-fish-nothobranchius-guentheri
#19
Tingting Liu, Long Ma, Zhaodi Zheng, Fenglin Li, Shan Liu, Yingbo Xie, Guorong Li
Resveratrol, SIRT1 activator, inhibits carcinogenesis predominantly performed in transgenic animal models, orthotopic cancers of nude mice or different cancer cell lines, but its effects during process of spontaneous tumors using vertebrate models remain untested. Spontaneous liver neoplasm is an age-related disease and is inhibited by resveratrol in the annual fish Nothobranchius guentheri, which indicates that the fish can act as an excellent model to study spontaneous tumorigenesis. Totally, 175 fish were fed with resveratrol and another 175 fish for controls...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901725/alamandine-reverses-hyperhomocysteinemia-induced-vascular-dysfunction-via-pka-dependent-mechanisms
#20
Tawar Qaradakhi, Minos Timotheos Matsoukas, Alan Hayes, Emma Rybalka, Martin Caprnda, Kvetoslava Rimarova, Milan Sepsi, Dietrich Büsselberg, Peter Kruzliak, John Matsoukas, Vasso Apostolopoulos, Anthony Zulli
INTRODUCTION: Hyperhomocysteinemia (HHcy) impairs nitric oxide endothelium-dependent vasodilation, consequently leading to atherosclerosis, a risk factor for cardiovascular disease. Novel treatments for HHcy are necessary. AIM: We tested the hypothesis that alamandine, a vasoactive peptide of the renin-angiotensin system (RAS), could reverse HHcy-induced vascular dysfunction through the MrgD receptor, and that this is mediated by the protein kinase A (PKA) pathway...
September 13, 2017: Cardiovascular Therapeutics
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