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https://www.readbyqxmd.com/read/29355521/the-dictyostelium-gsk3-kinase-glka-coordinates-signal-relay-and-chemotaxis-in-response-to-growth-conditions
#1
Jesus Lacal, Zhouxin Shen, Kimberly Baumgardner, Jing Wei, Steven P Briggs, Richard A Firtel
GSK3 plays a central role in orchestrating key biological signaling pathways, including cell migration. Here, we identify GlkA as a GSK3 family kinase with functions that overlap with and are distinct from those of GskA. We show that GlkA, as previously shown for GskA, regulates the cell's cytoskeleton through MyoII assembly and control of Ras and Rap1 function, leading to aberrant cell migration. However, there are both qualitative and quantitative differences in the regulation of Ras and Rap1 and their downstream effectors, including PKB, PKBR1, and PI3K, with glkA- cells exhibiting a more severe chemotaxis phenotype than gskA- cells...
January 16, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29353494/primary-liver-cancers-part-2-progression-pathways-and-carcinogenesis
#2
Kun Jiang, Barbara A Centeno
Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC) have been increasing in incidence worldwide and are leading causes of cancer death. Studies of the molecular alterations leading to these carcinomas provide insights into the key mechanisms involved. A literature review was conducted to identify articles with information relevant to current understanding of the etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory diseases are the key etiological risk factors for both HCC and ICC, although other diseases play a role, and for many ICCs, an underlying risk factor is not identified...
January 2018: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/29353317/tumor-suppressor-c-rassf-proteins
#3
REVIEW
Hiroaki Iwasa, Shakhawoat Hossain, Yutaka Hata
Human genome has ten genes that are collectedly called Ras association domain family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N-RASSF and C-RASSF encode Ras association domain-containing proteins and are frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF and N-RASSF are quite different. Six C-RASSF proteins (RASSF1-6) are characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo domain, while four N-RASSF proteins (RASSF7-10) lack it...
January 20, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29348819/recombinant-protein-of-haemonchus-contortus-small-gtpase-adp-ribosylation-factor-1-hcarf1-modulate-the-cell-mediated-immune-response-in-vitro
#4
Javaid Ali Gadahi, Muhammad Ehsan, Shuai Wang, Zhenchao Zhang, Ruofeng Yan, Xiaokai Song, Lixin Xu, Xiangrui Li
ADP-ribosylation factors (ARFs) are members of the Ras-related small GTPase family involved in the vesicular trafficking regulation. Immunomodulatory effects of these proteinson host cell arenot being addressed yet. H. contortus small GTPase ADP-ribosylation 1 gene (HcARF1) was cloned and recombinant protein of HcARF1 (rHcARF1) was successfully expressed in Escherichia coli. Binding activity of rHcARF1 to goat PBMCs was confirmed by immunofluorescence assay (IFA) and its immunomudulatory effects on cytokine secretion, cell proliferation, cell migration and nitric oxide production (NO) were observed by co-incubation of rHcARF1...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348127/murine-chronic-graft-versus-host-disease-proteome-profiling-discovers-ccl15-as-a-novel-biomarker-in-patients
#5
Jing Du, Ryan Flynn, Katelyn Paz, Hong-Gang Ren, Yuko Ogata, Qing Zhang, Philip R Gafken, Barry E Storer, Nathan H Roy, Janis K Burkhardt, Wendy Mathews, Jakub Tolar, Stephanie J Lee, Bruce R Blazar, Sophie Paczesny
Improved diagnostic and treatment methods are needed for chronic graft-versus-host disease (cGVHD), the leading cause of late non-relapse mortality (NRM) in long-term survivors of allogenic hematopoietic cell transplantation (allo-HCT). Validated biomarkers that facilitate disease diagnosis, and classification generally are lacking in cGVHD. Here, we conducted whole serum proteomics analysis of a well-established murine multi-organ system cGVHD model. We discovered 4 up-regulated proteins during cGVHD that are targetable by genetic ablation or blocking antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8 and CCL9 chemokines...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29346419/saxs-analysis-of-a-soluble-cytosolic-ngbr-construct-including-extracellular-and-transmembrane-domains
#6
Joshua Holcomb, Maysaa Doughan, Nicholas Spellmon, Brianne Lewis, Emerson Perry, Yingxue Zhang, Lindsey Nico, Junmei Wan, Srinivas Chakravarthy, Weifeng Shang, Qing Miao, Timothy Stemmler, Zhe Yang
The Nogo-B receptor (NgBR) is involved in oncogenic Ras signaling through directly binding to farnesylated Ras. It recruits farnesylated Ras to the non-lipid-raft membrane for interaction with downstream effectors. However, the cytosolic domain of NgBR itself is only partially folded. The lack of several conserved secondary structural elements makes this domain unlikely to form a complete farnesyl binding pocket. We find that inclusion of the extracellular and transmembrane domains that contain additional conserved residues to the cytosolic region results in a well folded protein with a similar size and shape to the E...
2018: PloS One
https://www.readbyqxmd.com/read/29344673/golph2-a-gene-downstream-of-ras-signaling-promotes-the-progression-of-pancreatic-ductal-adenocarcinoma
#7
Juan Duan, Xiaoguang Li, Shan Huang, Yanhua Zeng, Yan He, Hekun Liu, Dexin Lin, Dongdong Lu, Min Zheng
Various studies have previously demonstrated that Golgi protein-73 (GOLPH2) is overexpressed in tumorigenesis, which has been observed in hepatocellular carcinoma and prostate cancer. However, the expression levels and specific functions of GOLPH2 in the progression of pancreatic cancer remain to be elucidated. The present study aimed to investigate the expression of GOLPH2 in pancreatic ductal adenocarcinoma (PDAC) tissues and examined the effects of GOLPH2 on the growth and migration of pancreatic cancer cells...
January 15, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344173/rasal1-inhibits-hepg2-cell-growth-via-hif-2%C3%AE-mediated-gluconeogenesis
#8
Fanhua Meng, Wei Zhang, Yufeng Wang
RAS protein activator like 1 (RASAL1) is a member of the RAS GTPase-activating protein (GAP) family, and has been identified as a tumor suppressor in various types of cancer. In the present study, it was determined that decreased levels of RASAL1 were accompanied by a higher pathological stage and larger tumor size in human liver cancer. Therefore, it was hypothesized that RASAL1 may serve an inhibitory role in liver cancer. In the present study, the following was demonstrated: i) Exogenous expression of RASAL1 may inhibit the proliferation and invasion ability of HepG2 cells; ii) overexpression of RASAL1 may downregulate HIF-2α transcription activity and HIF-2α-mediated gluconeogenesis through extracellular signal-related kinase 1/2 activation; iii) RASAL1 may reduce the xenograft tumor size in nude mice by inhibiting the expression of hypoxia-inducible factor (HIF)-2α and gluconeogenesis enzymes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344147/systematic-analysis-of-the-molecular-mechanism-of-microrna-124-in-hepatoblastoma-cells
#9
Guiming Wang, Hong Liu, Zhigang Wei, Hongyan Jia, Yu Liu, Jiansheng Liu
The present study aimed to identify the molecular mechanisms of microRNA-124 (miRNA-124/miR-124) in hepatoblastoma. The GSE6207 microarray dataset, obtained from the Gene Expression Omnibus database, included samples extracted from HepG2 cells transfected with miR-124 duplex (the experimental group) or negative control (the control group) at 4, 8, 16, 24, 32, 72 and 120 h after transfection. Differentially expressed genes (DEGs) were screened between the two groups. miR-124 activity was inferred based on the expression of its target genes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343974/identification-of-key-pathways-and-genes-in-tp53-mutation-acute-myeloid-leukemia-evidence-from-bioinformatics-analysis
#10
Rui Huang, Xiwen Liao, Qiaochuan Li
Background: Tumor protein p53 (TP53) mutations are not only a risk factor in acute myeloid leukemia (AML) but also a potential biomarker for individualized treatment options. This study aimed to investigate potential pathways and genes associated with TP53 mutations in adult de novo AML. Methods: An RNA sequencing dataset of adult de novo AML was downloaded from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified by edgeR of the R platform...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29343748/sac7-and-rho1-regulate-the-white-to-opaque-switching-in-candida-albicans
#11
Siwy Ling Yang, Guisheng Zeng, Fong Yee Chan, Yan-Ming Wang, Dongliang Yang, Yue Wang
Candida albicans cells homozygous at the mating-type locus stochastically undergo the white-to-opaque switching to become mating-competent. This switching is regulated by a core circuit of transcription factors organized through interlocking feedback loops around the master regulator Wor1. Although a range of distinct environmental cues is known to induce the switching, the pathways linking the external stimuli to the central control mechanism remains largely unknown. By screening a C. albicans haploid gene-deletion library, we found that SAC7 encoding a GTPase-activating protein of Rho1 is required for the white-to-opaque switching...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343556/rasa1-nf1-mutant-lung-cancer-racing-to-the-clinic
#12
Shunsuke Kitajima, David A Barbie
Although mutation of NF1 has been described in non-small cell lung cancer (NSCLC), co-mutation with RASA1, another Ras-GTPase activating protein (RasGAP), defines a novel genetically defined subclass of NSCLC. RASA1/NF1 mutant cell lines are highly sensitive to MEK inhibitors, warranting clinical evaluation of MAPK inhibition in this subclass of patients.
January 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29342911/effects-of-acanthopanax-senticosus-on-brain-injury-induced-by-simulated-spatial-radiation-in-mouse-model-based-on-pharmacokinetics-and-comparative-proteomics
#13
Yingyu Zhou, Cuilin Cheng, Denis Baranenko, Jiaping Wang, Yongzhi Li, Weihong Lu
The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342140/atomic-structure-of-the-eukaryotic-intramembrane-ras-methyltransferase-icmt
#14
Melinda M Diver, Leanne Pedi, Akiko Koide, Shohei Koide, Stephen B Long
The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of the AAX residues and methylation of the exposed prenylcysteine residue at its terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that resides in the endoplasmic reticulum...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29340604/transient-recruitment-of-m-ras-gtpase-to-phagocytic-cups-in-raw264-macrophages-during-fc%C3%AE-r-mediated-phagocytosis
#15
Youhei Egami, Nobukazu Araki
M-Ras, a member of the Ras superfamily, is known to be involved in diverse cellular processes. However, its involvement in FcγR-mediated phagocytosis remains unknown. We examined the spatiotemporal localization of M-Ras during the engulfment of IgG-opsonized erythrocytes (IgG-Es) in RAW264 macrophages. By the live-cell imaging of fluorescent protein-fused M-Ras, we found that M-Ras was localized to the membrane of phagocytic cups during the early stage of phagosome formation. Notably, ratiometric image analysis revealed that M-Ras was concentrated in the membrane of forming phagosomes...
January 11, 2018: Microscopy
https://www.readbyqxmd.com/read/29340037/systemic-bioinformatics-analysis-of-recurrent-aphthous-stomatitis-gene-expression-profiles
#16
Jian Wu, Zheng-Ping Chen, An-Quan Shang, Wei-Wei Wang, Zong-Ning Chen, Yun-Juan Tao, Yue Zhou, Wan-Xiang Wang
Recurrent aphthous stomatitis (RAS) represents the most common chronic oral diseases with the prevalence ranges from 5% to 25% for different populations. Its pathogenesis remains poorly understood, which limits the development of effective drugs and treatment methods. In this study, we conducted systemic bioinformatics analysis of gene expression profiles from the Gene Expression Omnibus (GEO) to identify potential drug targets for RAS. We firstly downloaded the gene microarray datasets with the accession number of GSE37265 from GEO and performed robust multi-array (RMA) normalization with affy R programming package...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29336470/tnf-%C3%AE-induces-drp1-mediated-mitochondrial-fragmentation-during-inflammatory-cardiomyocyte-injury
#17
Yue-Liang Shen, Ying-Zhou Shi, Gai-Ge Chen, Lin-Lin Wang, Ming-Zhi Zheng, Hong-Feng Jin, Ying-Ying Chen
Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important process associated with cardiac dysfunction under different pathological conditions. The aim of the present study was to investigate the expression of Drpl during inflammatory myocardial injury. Sprague‑Dawley rats were treated intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2 cardiomyocytes were treated with LPS, interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α). Total and mitochondrial proteins were isolated from the heart tissue of rats and from the H9C2 cardiomyocytes...
January 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29335436/deregulated-pp1%C3%AE-phosphatase-activity-towards-mapk-activation-is-antagonized-by-a-tumor-suppressive-failsafe-mechanism
#18
Ming Chen, Lixin Wan, Jiangwen Zhang, Jinfang Zhang, Lourdes Mendez, John G Clohessy, Kelsey Berry, Joshua Victor, Qing Yin, Yuan Zhu, Wenyi Wei, Pier Paolo Pandolfi
The mitogen-activated protein kinase (MAPK) pathway is frequently aberrantly activated in advanced cancers, including metastatic prostate cancer (CaP). However, activating mutations or gene rearrangements among MAPK signaling components, such as Ras and Raf, are not always observed in cancers with hyperactivated MAPK. The mechanisms underlying MAPK activation in these cancers remain largely elusive. Here we discover that genomic amplification of the PPP1CA gene is highly enriched in metastatic human CaP. We further identify an S6K/PP1α/B-Raf signaling pathway leading to activation of MAPK signaling that is antagonized by the PML tumor suppressor...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29332338/x-ray-induced-epithelial-mesenchymal-transition-in-sw480-colorectal-cancer-cells-and-its-potential-mechanisms
#19
Suyong Lin, Shaoqin Chen, Zhihua Chen, Qibao Dai, Chunlin Ke
PURPOSE: The purpose of this study was to investigate the relation between X-ray irradiation and epithelial-mesenchymal transition (EMT), as well as the potential mechanisms of X-ray-induced EMT in SW480 colorectal cancer (CRC) cells. METHODS: It is well known that EMT plays a critical role in invasive and metastatic of colorectal cancer progression. However, the possible role of X-ray irradiation on EMT in colorectal cancer is widely disputed and its potential mechanisms are unclear...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331763/inhibition-of-isoprenylcysteine-carboxylmethyltransferase-sensitizes-common-chemotherapies-in-cervical-cancer-via-ras-dependent-pathway
#20
Qin Pan, Rong Liu, Hasina Banu, Liang Ma, Hui Li
Isoprenylcysteine carboxylmethyltransferase (Icmt) catalyzes the last step of post-translational protein prenylation, which is essential for the stability and proper functions of many oncogenic proteins, such as Ras. Despite extensive studies on the roles of Icmt in tumor transformation and progression, little is known on the involvement ofIcmt in the development of tumor resistance to chemotherapy. Here we show the upregulation of Icmt as a persistent response to chemotherapy in cervical cancer cells. In-depth functional analysis demonstrated that Icmt inhibition significantly inhibited growth, induced apoptosis and augmented the inhibitory effects of chemotherapy drugs in cervical cancer in cell culture system and xenograft mouse model...
January 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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