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https://www.readbyqxmd.com/read/27913681/the-borg-family-of-cdc42-effector-proteins-cdc42ep1-5
#1
REVIEW
Aaron J Farrugia, Fernando Calvo
Despite being discovered more than 15 years ago, the Borg (binder of Rho GTPases) family of Cdc42 effector proteins (Cdc42EP1-5) remains largely uncharacterised and relatively little is known about their structure, regulation and role in development and disease. Recent studies are starting to unravel some of the key functional and mechanistic aspects of the Borg proteins, including their role in cytoskeletal remodelling and signalling. In addition, the participation of Borg proteins in important cellular processes such as cell shape, directed migration and differentiation is slowly emerging, directly linking Borgs with important physiological and pathological processes such as angiogenesis, neurotransmission and cancer-associated desmoplasia...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911772/c-terminal-domain-ctd-phosphatase-links-rho-gtpase-signaling-to-pol-ii-ctd-phosphorylation-in-arabidopsis-and-yeast
#2
Bo Zhang, Guohua Yang, Yu Chen, Yihong Zhao, Peng Gao, Bo Liu, Haiyang Wang, Zhi-Liang Zheng
Rho GTPases, including the Rho, Cdc42, Rac, and ROP subfamilies, act as pivotal signaling switches in various growth and developmental processes. Compared with the well-defined role of cytoskeletal organization in Rho signaling, much less is known regarding transcriptional regulation. In a mutant screen for phenotypic enhancers of transgenic Arabidopsis plants expressing a constitutively active form of ROP2 (designated CA1-1), we identified RNA polymerase II (Pol II) C-terminal domain (CTD) phosphatase-like 1 (CPL1) as a transcriptional regulator of ROP2 signaling...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27904039/role-of-rac1-wave2-signaling-in-mediating-the-inhibitory-effects-of-%C3%AE-tocotrienol-on-mammary-cancer-cell-migration-and-invasion
#3
Ibrahim Gayadh Algayadh, Venkateshwararao Dronamraju, Paul William Sylvester
The majority of breast cancer deaths result from the progression of this disease to a metastatic phenotype. Rac1 and Cdc42 are Rho family members that together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, play an important role in cytoskeletal reorganization and the formation of membrane protrusions that promote cancer cell migration and invasion. γ-Tocotrienol, is a natural isoform within the vitamin E family of compounds that inhibits breast cancer cell growth and progression by suppressing various signaling pathways involved in mitogenic signaling and metastatic progression...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#4
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901125/rab14-specifies-the-apical-membrane-through-arf6-mediated-regulation-of-lipid-domains-and-cdc42
#5
Ruifeng Lu, Jean M Wilson
The generation of cell polarity is essential for the development of multi-cellular organisms as well as for the function of epithelial organs in the mature animal. Small GTPases regulate the establishment and maintenance of polarity through effects on cytoskeleton, membrane trafficking, and signaling. Using short-term 3-dimensional culture of MDCK cells, we find that the small GTPase Rab14 is required for apical membrane specification. Rab14 knockdown results in disruption of polarized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical membrane...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895229/influence-of-pecam-1-ligand-interactions-on-pecam-1-dependent-cell-motility-and-filopodia-extension
#6
Valsamma Abraham, Andrew Parambath, Debria S Joe, Horace M DeLisser
Platelet endothelial cell adhesion molecule (PECAM-1) has been implicated in angiogenesis through processes that involve stimulation of endothelial cell motility. Previous studies suggest that PECAM-1 tyrosine phosphorylation mediates the recruitment and then activation of the tyrosine phosphatase SHP-2, which in turn promotes the turnover of focal adhesions and the extension of filopodia, processes critical to cell motility. While these studies have implicated PECAM-1-dependent signaling in PECAM-1-mediated cell motility, the involvement of PECAM-1 ligand binding in cell migration is undefined...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27890731/mechanisms-of-cdc42-mediated-rat-msc-differentiation-on-micro-nano-textured-topography
#7
Guangwen Li, Yanyan Song, Mengqi Shi, Yuanhong Du, Wei Wang, Yumei Zhang
Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/ β -catenin is the underlying mechanism...
November 24, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27886249/impairment-of-pdgf-induced-chemotaxis-by-extracellular-%C3%AE-synuclein-through-selective-inhibition-of-rac1-activation
#8
Taro Okada, Chihoko Hirai, Shaymaa Mohamed Mohamed Badawy, Lifang Zhang, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is characterized by α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies. Although it is known that extracellular α-Syn is detected in the plasma and cerebrospinal fluid, its physiological significance remains unclear. Here, we show that extracellular α-Syn suppresses platelet-derived growth factor (PDGF)-induced chemotaxis in human neuroblastoma SH-SY5Y cells. The inhibitory effect was stronger in the mutant α-Syn(A53T), found in hereditary PD, and the degree of inhibition was time-dependent, presumably because of the oligomerization of α-Syn...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885255/tfap2c-mediated-upregulation-of-tgfbr1-promotes-lung-tumorigenesis-and-epithelial-mesenchymal-transition
#9
Wanyeon Kim, EunGi Kim, Sungmin Lee, Daehoon Kim, Jahyun Chun, Kang Hyun Park, HyeSook Youn, BuHyun Youn
TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression...
November 25, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27880081/an-emerging-role-for-iqgap1-in-tight-junction-control
#10
Barbara E Tanos, Charles Yeaman, Enrique Rodriguez-Boulan
IQGAP1 is a scaffold protein involved in the assembly of adherens junctions. Our work has recently revealed a novel role for IQGAP1 in the regulation of tight junctions (TJ) through differential recruitment of claudins to the nascent TJ. Here, we discuss the potential mechanisms of this regulation, including IQGAP1 effects on CDC42, and IQGAP1 interactions with sorting/trafficking molecules (e.g. Exo70). Given the many roles of IQGAP1 and the large number of interacting partners, we focus our discussion of these functions in the context of junction formation, trafficking, growth factor signaling and cancer...
November 23, 2016: Small GTPases
https://www.readbyqxmd.com/read/27865965/palladin-is-involved-in-platelet-activation-and-arterial-thrombosis
#11
Xuejiao Chen, Xuemei Fan, Juan Tan, Panlai Shi, Xiyi Wang, Jinjin Wang, Ying Kuang, Jian Fei, Junling Liu, Suying Dang, Zhugang Wang
The dynamics of actin cytoskeleton have been shown to play a critical role during platelet activation. Palladin is an actin-associated protein, serving as a cytoskeleton scaffold to bundle actin fibers and actin cross linker. The functional role of palladin on platelet activation has not been investigated. Here, we characterized heterozygous palladin knockout (palladin(+/-)) mice to elucidate the platelet-related functions of palladin. The results showed that palladin was expressed in platelets and moderate palladin deficiency accelerated hemostasis and arterial thrombosis...
November 10, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27865799/oleic-acid-induced-angptl4-enhances-head-and-neck-squamous-cell-carcinoma-anoikis-resistance-and-metastasis-via-up-regulation-of-fibronectin
#12
Chih-Jie Shen, Shih-Hung Chan, Chung-Ta Lee, Wan-Chen Huang, Jhih-Peng Tsai, Ben-Kuen Chen
Obese patients have higher levels of free fatty acids (FFAs) in their plasma and a higher risk of cancer than their non-obese counterparts. However, the mechanisms involved in the regulation of cancer metastasis by FFAs remain unclear. In this study, we found that oleic acid (OA) induced angiopoietin-like 4 (ANGPTL4) protein expression and secretion and conferred anoikis resistance to head and neck squamous cell carcinomas (HNSCCs). The autocrine production of OA-induced ANGPTL4 further promoted HNSCC migration and invasion...
November 16, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27864650/heme-oxygenase-1-protects-spinal-cord-neurons-from-hydrogen-peroxide-induced-apoptosis-via-suppression-of-cdc42-mlk3-mkk7-jnk3-signaling
#13
Siyuan Wang, Tao Zhang, Zhen Yang, Jianhua Lin, Bin Cai, Qingfeng Ke, Wenbin Lan, Jinxing Shi, Shiqiang Wu, Wenping Lin
The mechanisms by which oxidative stress induces spinal cord neuron death has not been completely understood. Investigation on the molecular signal pathways involved in oxidative stress-mediated neuronal death is important for development of new therapeutics for oxidative stress-associated spinal cord disorders. In current study we examined the role of heme oxygenase-1 (HO-1) in the modulation of MLK3/MKK7/JNK3 signaling, which is a pro-apoptotic pathway, after treating primary spinal cord neurons with H2O2...
November 18, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27863394/mda-9-syntenin-sdcbp-modulates-small-gtpases-rhoa-and-cdc42-via-transforming-growth-factor-%C3%AE-1-to-enhance-epithelial-mesenchymal-transition-in-breast-cancer
#14
Mitchell E Menezes, Xue-Ning Shen, Swadesh K Das, Luni Emdad, Devanand Sarkar, Paul B Fisher
Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating cancer invasion and metastasis. However, the molecular mechanisms underlying this transition require further clarification. MDA-9/syntenin (SDCBP) expression is elevated in breast cancer patient samples as well as cultured breast cancer cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more epithelial-like phenotype, along with changes in EMT markers, cytoskeletal rearrangement and decreased invasion...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27862857/casticin-induced-apoptotic-cell-death-and-altered-associated-gene-expression-in-human-colon-cancer-colo-205-cells
#15
Hung-Sheng Shang, Jia-You Liu, Hsu-Feng Lu, Han-Sun Chiang, Chia-Hain Lin, Ann Chen, Yuh-Feng Lin, Jing-Gung Chung
Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca(2+) productions, level of mitochondria membrane potential (ΔΨm ) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death...
November 14, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27852900/gradients-of-phosphatidylserine-contribute-to-plasma-membrane-charge-localization-and-cell-polarity-in-fission-yeast
#16
Armin Haupt, Nicolas Minc
Surface charges at the inner leaflet of the plasma membrane may contribute to regulate the surface recruitment of key signaling factors. Phosphatidylserine (PS) is an abundant charged lipid, which may regulate charge distribution in different cell types. In here, we characterize the subcellular distribution and function of PS in the rod-shaped, polarized fission yeast. We find that PS preferably accumulates at cell tips and defines a gradient of negative charges along the cell surface. This polarization depends on actin-mediated endocytosis and contributes to the subcellular partitioning of charged polarity-regulating Rho-GTPases like Rho1 or Cdc42 in a protein charge-dependent manner...
November 16, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27852748/quantitative-gtpase-affinity-purification-identifies-rho-family-protein-interaction-partners
#17
Florian E Paul, Henrik Zauber, Laura von Berg, Oliver Rocks, Oliver Daumke, Matthias Selbach
Although Rho GTPases are essential molecular switches involved in many cellular processes, an unbiased experimental comparison of their interaction partners was not yet performed. Here, we develop quantitative GTPase affinity purification (qGAP) to systematically identify interaction partners of six Rho GTPases (Cdc42, Rac1, RhoA, RhoB, RhoC, RhoD) depending on their nucleotide loading state. The method works with cell line or tissue-derived protein lysates in combination with SILAC-based or label free quantification, respectively...
November 16, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27849309/activation-of-rac1-and-rhoa-preserve-corneal-endothelial-barrier-function
#18
María C Ortega, Diana Santander-García, Beatriz Marcos-Ramiro, Susana Barroso, Susan Cox, Ignacio Jiménez-Alfaro, Jaime Millán
Purpose: The corneal endothelium is responsible for the correct hydration of the corneal stroma. Corneal endothelial cells have a low proliferative capacity, so preserving their barrier function under suboptimal conditions that cause osmotic imbalance, such as those arising from corneal pathologies, age, cryopreservation, and transplantation, is essential for maintaining corneal transparency. We have investigated the signaling induced by hyperosmotic shock that reversibly disrupts corneal endothelial barriers in human endothelial cells and in murine corneas...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27846191/noncoding-transcribed-ultraconserved-region-t-ucr-uc-261-participates-in-intestinal-mucosa-barrier-damage-in-crohn-s-disease
#19
Xiao Xian Qian, Jiang Chen Peng, An Tao Xu, Di Zhao, Yu Qi Qiao, Tian Rong Wang, Jun Shen, Zhi Hua Ran
BACKGROUND: To date, 481 ultraconserved regions (UCRs) have been discovered in human genome. We aimed to investigate the transcribed UCR (T-UCR) characteristics in Crohn's disease (CD ) and determine whether T-UCR uc.261 participated in intestinal mucosa barrier damage. METHODS: T-UCRs were screened in active CD mucosa using the Arraystar Human T-UCR Microarray and validated with quantitative real-time reverse transcription PCR, together with tight junction proteins (TJPs) including junctional adhesion molecule-A, occludin, claudin-1, and zonula occluden-1...
December 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27835612/stimulus-dependent-dissociation-between-xb130-and-tks5-scaffold-proteins-promotes-airway-epithelial-cell-migration
#20
Serisha Moodley, Mathieu Derouet, Xiao Hui Bai, Feng Xu, Andras Kapus, Burton B Yang, Mingyao Liu
Repair of airway epithelium after injury requires migration of neighboring epithelial cells to injured areas. However, the molecular mechanisms regulating airway epithelial cell migration is not well defined. We have previously shown that XB130, a scaffold protein, is required for airway epithelial repair and regeneration in vivo, and interaction between XB130 and another scaffold protein, Tks5, regulates cell proliferation and survival in human bronchial epithelial cells. The objective of the present study was to determine the role of XB130 and Tks5 interaction in airway epithelial cell migration...
November 9, 2016: Oncotarget
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