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Ras protein

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https://www.readbyqxmd.com/read/28732393/microrna-30a-suppresses-tumor-progression-by-blocking-ras-raf-mek-erk-signaling-pathway-in-hepatocellular-carcinoma
#1
Kun Zhou, Xiaoyu Luo, Yu Wang, Dachun Cao, Gang Sun
Emerging reports suggest microRNAs (miRNAs) play a vital role in the progression of malignant tumors. MiR-30a is downregulated in a variety of cancers and acts as a tumor suppressing gene. However, the molecular mechanisms of miRNA-30a in hepatocellular carcinoma (HCC) are still unclear. Hereby, in this study, we detected that miR-30a expression was significantly down-regulated in both HCC tissues compared with adjacent non-cancerous liver tissues, and we also observed that miR-30a expression was lower in HCC cell lines than that of normal controls...
July 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28732359/resveratrol-inhibits-age-dependent-spontaneous-tumorigenesis-by-sirt1-mediated-post-translational-modulations-in-the-annual-fish-nothobranchius-guentheri
#2
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...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731157/curcumin-prevents-lipopolysaccharide-induced-matrix-metalloproteinase%C3%A2-2-activity-via-the-ras-mek1-2-signaling-pathway-in-rat-vascular-smooth-muscle-cells
#3
Yi Zhong, Jian Feng, Jiafu Li, Zhongcai Fan
The aim of the present study was to examine the effect of curcumin treatment on lipopolysaccharide (LPS)-induced matrix metalloproteinase‑2 (MMP‑2) activity, and assess whether the effects are mediated by the Ras/mitogen‑activated protein kinase kinase 1/2 (MEK1/2) signaling pathway in vascular smooth muscle cells (VSMCs). VSMCs were isolated from male Sprague‑Dawley rats. Protein expression levels were analyzed by western blotting. The activity of MMP‑2 was measured with gelatin zymography, and an electrophoretic mobility shift assay was used to detect the DNA binding activity of nuclear factor‑κB (NF‑κB)...
July 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28729758/analysis-of-correlated-mutations-in-ras-g-domain
#4
Ekta Pathak
Ras GTPases are most prevalent proto-oncogenes in human cancer. Mutations in Ras remain untreatable more than three decades after the initial discovery. At the amino acid level, some residues under physical or functional constraints exhibit correlated mutations also known as coevolving/covariant residues. Revealing intra-molecular co-evolution between amino acid sites of proteins has become an emerging area of research as it enlightens the importance of variable regions. Here, I have identified and analyzed the coevolving residues in the Ras GTP binding domain (G-domain)...
2017: Bioinformation
https://www.readbyqxmd.com/read/28729421/the-small-g-protein-ras2-is-involved-in-the-metabolic-compensation-of-the-circadian-clock-in-the-circadian-model-neurospora-crassa
#5
Norbert Gyöngyösi, Anita Szöke, Krisztina Ella, Krisztina Káldi
Accumulating evidence from both experimental and clinical investigations indicate a tight interaction between metabolism and circadian timekeeping; however, knowledge of the underlying mechanism is still incomplete. Metabolic compensation allows circadian oscillators to run with a constant speed at different substrate levels and therefore is a substantial criterion of a robust rhythm in a changing environment. Because previous data have suggested a central role of RAS2-mediated signaling in the adaptation of yeast to different nutritional environments, we examined the involvement of RAS2 in the metabolic regulation of the clock in the circadian model organism Neurospora crassa...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28729416/cib2-negatively-regulates-oncogenic-signaling-in-ovarian-cancer-via-sphingosine-kinase-1
#6
Wenying Zhu, Kate E Jarman, Noor A Lokman, Heidi A Neubauer, Lorena T Davies, Briony L Gliddon, Houng Taing, Paul A B Moretti, Martin K Oehler, Melissa R Pitman, Stuart M Pitson
Sphingosine kinase 1 (SK1) is a key regulator of the cellular balance between pro-apoptotic and pro-survival sphingolipids. Oncogenic signaling by SK1 relies on its localization to the plasma membrane, which is mediated by the calcium and integrin binding protein CIB1 via its Ca(2+)-myristoyl switch function. Here we show that another member of the CIB family, CIB2, plays a surprisingly opposite role to CIB1 in the regulation of SK1 signalling. CIB2 bound SK1 on the same site as CIB1, yet it lacks the Ca(2+)-myristoyl switch function...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28728573/splicing-arrays-reveal-novel-rbm10-targets-including-smn2-pre-mrna
#7
Leslie C Sutherland, Philippe Thibault, Mathieu Durand, Elvy Lapointe, Jose M Knee, Ariane Beauvais, Irina Kalatskaya, Sarah C Hunt, Julie J Loiselle, Justin G Roy, Sarah J Tessier, Gustavo Ybazeta, Lincoln Stein, Rashmi Kothary, Roscoe Klinck, Benoit Chabot
BACKGROUND: RBM10 is an RNA binding protein involved in message stabilization and alternative splicing regulation. The objective of the research described herein was to identify novel targets of RBM10-regulated splicing. To accomplish this, we downregulated RBM10 in human cell lines, using small interfering RNAs, then monitored alternative splicing, using a reverse transcription-PCR screening platform. RESULTS: RBM10 knockdown (KD) provoked alterations in splicing events in 10-20% of the pre-mRNAs, most of which had not been previously identified as RBM10 targets...
July 20, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28728277/-effects-of-pi3k%C3%AE-rhoa-pathway-on-phagocytosis-defect-of-alveolar-macrophages-in-a-mouse-model-of-chronic-obstructive-pulmonary-disease
#8
S T Hu, Q Xia, X L Zeng, H R Bao, X J Liu
Objective: To investigate effects of Phosphoinositide3-Kinases (PI3Kδ)-Ras homolog gene family member A(RhoA) pathway on phagocytosis deficiency of alveolar macrophages (AMs) in a mouse model of chronic obstructive pulmonary disease (COPD). Methods: Twenty mice were exposed to cigarette smoking to establish the COPD model, with 20 mice as the control group. AMs were isolated from lung tissue by discontinuous density gradient centrifugation and then divided into a healthy control group, a COPD group, a healthy IC87114 group and a COPD IC87114 group...
July 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28724936/an-engineered-protein-antagonist-of-k-ras-b-raf-interaction
#9
Monique J Kauke, Michael W Traxlmayr, Jillian A Parker, Jonathan D Kiefer, Ryan Knihtila, John McGee, Greg Verdine, Carla Mattos, K Dane Wittrup
Ras is at the hub of signal transduction pathways controlling cell proliferation and survival. Its mutants, present in about 30% of human cancers, are major drivers of oncogenesis and render tumors unresponsive to standard therapies. Here we report the engineering of a protein scaffold for preferential binding to K-Ras G12D. This is the first reported inhibitor to achieve nanomolar affinity while exhibiting specificity for mutant over wild type (WT) K-Ras. Crystal structures of the protein R11.1.6 in complex with K-Ras WT and K-Ras G12D offer insight into the structural basis for specificity, highlighting differences in the switch I conformation as the major defining element in the higher affinity interaction...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724604/a-simple-toolset-to-identify-endogenous-post-translational-modifications-for-a-target-protein-a-snapshot-of-the-egfr-signaling-pathway
#10
Henrick Horita, Andy Law, Soonjin Hong, Kim Middleton
Identification of a novel post-translational modification (PTM) for a target protein, defining its physiologic role, and studying its potential crosstalk with other PTMs is a challenging process. A set of highly sensitive tools termed Signal-Seeker kits was developed, which enables rapid and simple detection of post-translational modifications on any target protein.  The methodology for these tools utilizes affinity purification of modified proteins from a cell or tissue lysate and immunoblot analysis. These tools utilize a single lysis system that is effective at identifying endogenous, dynamic PTM changes, as well as the potential crosstalk between PTMs...
July 19, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#11
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28720877/role-of-the-histone-deacetylase-inhibitor-valproic-acid-in-high-fat-diet-induced-hypertension-via-inhibition-of-hdac1-angiotensin-ii-axis
#12
J Choi, S Y Park, T K Kwon, S-I Sohn, K M Park, J I Kim
BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice...
July 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28719146/natural-compounds-in-cancer-prevention-effects-of-coffee-extracts-and-their-main-polyphenolic-component-5-cqa-on-oncogenic-ras-proteins
#13
Alessandro Palmioli, Carlotta Cairamelli, Renata Tisi, Michela Spinelli, Gaia De Sanctis, Elena Sacco, Cristina Airoldi
Recent epidemiological studies demonstrate that consumption of healthy foods, especially rich in polyphenols content, might reduce the incidence of cancer and degenerative diseases. In particular, chlorogenic acids (CGAs) occur ubiquitously in food, representing the most abundant polyphenols in the human diet. A number of CGA beneficial biological effects, including anti-inflammatory activity, anti-carcinogenic activity and protection against neurodegenerative diseases have been reported. However, the molecular mechanisms at the basis of these biological activities have not yet been investigated in depth...
July 18, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28713987/angiotensin%C3%A2-1%C3%A2-7-attenuates-caerulein%C3%A2-induced-pancreatic-acinar-cell-apoptosis
#14
Lijian Cui, Ruixia Liu, Chunyun Li, Xiaozheng Yu, Xiaoya Liu, Fei Hou, Cheng Chi, Chenghong Yin, Chao Wang
Extensive apoptosis of pancreatic acinar cells frequently occurs in acute pancreatitis (AP), and has been identified to be closely associated with the decrease of pancreatic parenchymal cells and pancreatic damage. The present study aimed to investigate the possible effect of angiotensin (Ang)‑(1‑7) on caerulein (CAE)‑induced pancreatic acinar cell apoptosis. Mouse pancreatic acinar cancer cells (MPC‑83) were divided into 4 groups: Control group; CAE group; CAE + Ang‑(1‑7) group; and CAE + Ang‑(1‑7) antagonist (A779) group...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712408/-dectection-of-g3bp-and-cd44v6-in-the-tissues-of-laryngeal-squamous-cell-carcinoma-and-their-clinical-significance
#15
Dahu Luo, Weihua Lou
Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28710284/the-neuronal-protein-neurexin-directly-interacts-with-the-scribble-pix-complex-to-stimulate-f-actin-assembly-for-synaptic-vesicle-clustering
#16
Menglong Rui, Jinjun Qian, Lijuan Liu, Yihan Cai, Huihui Lv, Junhai Han, Zhengping Jia, Wei Xie
Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neuro-transmission. However, how SV cluster in particular synaptic compartments to maintain normal neurotransmitter release remains a mystery. The presynaptic protein Neurexin (NRX) plays a significant role in synaptic architecture and function, and some evidences suggest that NRX is associated with neurological disorders, including autism spectrum disorders. However, the role of NRX in SV clustering is unclear...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28710070/tnf-%C3%AE-receptor-1-knockdown-in-subfornical-organ-ameliorates-sympathetic-excitation-and-cardiac-hemodynamics-in-heart-failure-rats
#17
Yang Yu, Shun-Guang Wei, Robert M Weiss, Robert B Felder
In systolic heart failure (HF), circulating proinflammatory cytokines upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain, contributing to sympathetic excitation and cardiac dysfunction. Important among these is the subfornical organ (SFO), a forebrain circumventricular organ that lacks an effective blood-brain barrier and senses circulating humors. We hypothesized that the tumor necrosis factor-α (TNF-α) receptor 1 (TNFR1) in the SFO contributes to sympathetic excitation and cardiac dysfunction in HF rats...
July 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#18
REVIEW
Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli
The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF...
July 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28707374/localization-and-functional-analysis-of-the-insect-specific-rabx4-in-the-brain-of-bombyx-mori
#19
Tomohide Uno, Masayuki Furutani, Katsuhiko Sakamoto, Yuichi Uno, Kengo Kanamaru, Akira Mizoguchi, Susumu Hiragaki, Makio Takeda
Rab proteins are small monomeric GTPases/GTP-binding proteins, which form the largest branch of the Ras superfamily. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they function as regulators of distinct steps in membrane trafficking. RabX4 is an insect-specific Rab protein that has no close homolog in vertebrates. There is little information about insect-specific Rab proteins. RabX4 was expressed in Escherichia coli and subsequently purified. Antibodies against Bombyx mori RabX4 were produced in rabbits for western immunoblotting and immunohistochemistry...
July 14, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28706206/identification-of-long-non-coding-rnas-in-two-anthozoan-species-and-their-possible-implications-for-coral-bleaching
#20
Chen Huang, Jean-Étienne R L Morlighem, Jing Cai, Qiwen Liao, Carlos Daniel Perez, Paula Braga Gomes, Min Guo, Gandhi Rádis-Baptista, Simon Ming-Yuen Lee
Long non-coding RNAs (lncRNAs) have been shown to play regulatory roles in a diverse range of biological processes and are associated with the outcomes of various diseases. The majority of studies about lncRNAs focus on model organisms, with lessened investigation in non-model organisms to date. Herein, we have undertaken an investigation on lncRNA in two zoanthids (cnidarian): Protolpalythoa varibilis and Palythoa caribaeorum. A total of 11,206 and 13,240 lncRNAs were detected in P. variabilis and P. caribaeorum transcriptome, respectively...
July 13, 2017: Scientific Reports
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