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Cdc42

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https://www.readbyqxmd.com/read/28539409/spatial-analysis-of-cdc42-activity-reveals-a-role-for-plasma-membrane-associated-cdc42-in-centrosome-regulation
#1
Kari A Herrington, Andrew L Trinh, Carolyn Dang, Ellen O'Shaughnessy, Klaus M Hahn, Enrico Gratton, Michelle A Digman, Christine Sütterlin
The ability of the small GTPase Cdc42 to regulate diverse cellular processes depends on tight spatial control of its activity. Cdc42 function is best understood at the plasma membrane (PM), where it regulates cytoskeletal organization and cell polarization. Active Cdc42 has also been detected at the Golgi, but its role and regulation at this organelle is only partially understood. Here we analyze the spatial distribution of Cdc42 activity by monitoring the dynamics of the Cdc42 FLARE biosensor using the phasor approach to FLIM-FRET...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539360/a-dock-and-coalesce-mechanism-driven-by-hydrophobic-interactions-governs-cdc42-binding-with-its-effector-protein-ack
#2
George J N Tetley, Helen R Mott, R Neil Cooley, Darerca Owen
Cdc42 is a Rho-family small G protein that has been widely studied for its role in controlling the actin cytoskeleton and plays a part in several potentially oncogenic signalling networks. Similar to most other small G proteins, Cdc42 binds to many downstream effector proteins to elicit its cellular effects. These effector proteins all engage the same face of Cdc42, the conformation of which is governed by the activation state of the G protein. Previously, the importance of individual residues in conferring binding affinity has been explored for residues within Cdc42 for three of its CRIB effectors, activated Cdc42 kinase (ACK), p21-activated kinase (PAK), and Wiskott-Aldrich syndrome protein (WASP)...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28527113/mutant-p53-promotes-cell-spreading-and-migration-via-arhgap44
#3
Jinjin Xu, Jian Jiao, Wei Xu, Lei Ji, Dongjie Jiang, Shaofang Xie, Syeda Kubra, Xiaotao Li, Junjiang Fu, Jianru Xiao, Bianhong Zhang
The tumor suppressor p53 protein is either lost or mutated in about half of all human cancers. Loss of p53 function is well known to influence cell spreading, migration and invasion. While expression of mutant p53 is not equivalent to p53 loss, mutant p53 can acquire new functions to drive cell spreading and migration via different mechanisms. In our study, we found that mutant p53 significantly increased cell spreading and migration when comparing with p53-null cells. RNA-Seq analysis suggested that Rho GTPase activating protein 44 (ARHGAP44) is a new target of mutant p53, which suppressed ARHGAP44 transcription...
May 16, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28521487/microrna-29a-functions-as-a-potential-tumor-suppressor-through-directly-targeting-cdc42-in-non-small-cell-lung-cancer
#4
Yongqiang Li, Zhi Wang, Yijiang Li, Ruijun Jing
The expression and function of microRNA-29a (miR-29a) have been investigated in various types of cancer. In the present study, the expression, function and underlying molecular mechanism of miR-29a were investigated in non-small cell lung cancer (NSCLC). The expression level of miR-29a in NSCLC was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration and invasion ability were determined using Cell Counting Kit-8, cell migration and invasion assays, respectively...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520772/the-chicken-embryo-as-an-efficient-model-to-test-the-function-of-muscle-fusion-genes-in-amniotes
#5
Daniel Sieiro, Nadège Véron, Christophe Marcelle
The fusion of myoblasts into multinucleated myotubes is a crucial step of muscle growth during development and of muscle repair in the adult. While multiple genes were shown to play a role in this process, a vertebrate model where novel candidates can be tested and analyzed at high throughput and relative ease has been lacking. Here, we show that the early chicken embryo is a fast and robust model in which functional testing of muscle fusion candidate genes can be performed. We have used known modulators of muscle fusion, Rac1 and Cdc42, along with the in vivo electroporation of integrated, inducible vectors, to show that the chicken embryo is a suitable model in which their function can be tested and quantified...
2017: PloS One
https://www.readbyqxmd.com/read/28506239/dihydroartemisinin-inhibits-tctp-dependent-metastasis-in-gallbladder-cancer
#6
Fei Zhang, Qiang Ma, Zihang Xu, Haibin Liang, Huaifeng Li, Yuanyuan Ye, Shanshan Xiang, Yijian Zhang, Lin Jiang, Yunping Hu, Zheng Wang, Xuefeng Wang, Yong Zhang, Wei Gong, Yingbin Liu
BACKGROUND: Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer. METHODS: Levels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins...
May 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28502648/control-of-astrocyte-morphology-by-rho-gtpases
#7
REVIEW
Andre Zeug, Franziska E Müller, Stefanie Anders, Michel K Herde, Daniel Minge, Evgeni Ponimaskin, Christian Henneberger
Astrocytes modulate and support neuronal and synapse function via numerous mechanisms that often rely on diffusion of signalling molecules, ions or metabolites through extracellular space. As a consequence, the spatial arrangement and the distance between astrocyte processes and neuronal structures is of functional importance. Likewise, changes of astrocyte structure will affect the ability of astrocytes to interact with neurons. In contrast to neurons, where rapid morphology changes are critically involved in many aspects of physiological brain function, a role of astrocyte restructuring in brain physiology is only beginning to emerge...
May 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28498918/expression-and-activity-of-the-small-rhogtpase-cdc42-in-blood-cells-of-older-adults-are-associated-with-age-and-cardiovascular-disease
#8
M Carolina Florian, Jochen Klenk, Gina Marka, Karin Soller, Hady Kiryakos, Richard Peter, Florian Herbolsheimer, Dietrich Rothenbacher, Michael Denkinger, Hartmut Geiger
The small RhoGTPase Cdc42 is mechanistically linked to aging of multiple tissues and to rejuvenation of hematopoietic stem cells (HSCs) in mice. However, data validating Cdc42 activity and expression as biomarker for aging in humans are still missing. Here we hypothesized that Cdc42 might serve as a novel biomarker of aging in older adults and therefore we determined Cdc42 activity and expression levels in peripheral blood (PB) cells from a cohort of 196 donors. We investigated the association of these parameters with both chronological and biological aging...
May 12, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28498804/increased-s100a15-expression-and-decreased-dna-methylation-of-its-gene-promoter-are-involved-in-high-metastasis-potential-and-poor-outcome-of-lung-adenocarcinoma
#9
Yung-Che Chen, Meng-Chih Lin, Chang-Chun Hsiao, Yi-Xin Zheng, Kuang-Den Chen, Ming-Tse Sung, Chung-Jen Chen, Ting-Ya Wang, Yong-Yong Lin, Huang-Chih Chang, Yu-Mu Chen, Jen-Chieh Chang
PURPOSE: This study aims to determine the functional role of S100A15 and its promoter DNA methylation patterns in lung cancer progression. EXPERIMENTAL DESIGN: We analyzed 178 formalin-fixed paraffin embedded specimens from lung cancer patients, including 24 early stage and 91 advanced stage adenocarcinoma. S100A15 protein expression was evaluated by immunohistochemistry stain, and its DNA methylation levels were measured by pyrosequencing. RESULTS: S100A15 nuclear staining was increased in lung adenocarcinoma patients with distant metastasis versus those without distant metastasis...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28489964/specific-activation-of-plekhg2-induced-serum-response-element-dependent-gene-transcription-by-four-and-a-half-lim-domains-fhl-1-but-not-fhl2-or-fhl3
#10
Masashi Nishikawa, Katsuya Sato, Shun Nakano, Hisashi Yamakawa, Takahiro Nagase, Hiroshi Ueda
PLEKHG2 is a Gβγ- and Gαs-dependent guanine nucleotide exchange factor for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways such as those for actin cytoskeletal reorganization and serum response element (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the other FHL family members and found that the FHL1A specifically regulate the PLEKHG2 activity. Moreover, FHL1A further enhanced Gβγ- and PLEKHG2-induced SRE-dependent gene transcription, whereas FHL1A partially restored the attenuated PLEKHG2-induced SRE-dependent gene transcription by Gαs...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28489401/molecular-dynamics-markov-state-model-of-protein-ligand-binding-and-allostery-in-crib-pdz-conformational-selection-and-induced-fit
#11
Kelly M Thayer, Bharat Lakhani, David L Beveridge
Conformational selection and induced fit are well-known contributors to ligand binding and allosteric effects in proteins. Molecular dynamics (MD) simulations now enable the theoretical study of protein-ligand binding in terms of ensembles of interconverting microstates and the population shifts characteristic of "dynamical allostery." Here we investigate protein-ligand binding and allostery based on a Markov state model (MSM) with states and rates obtained from all-atom MD simulations. As an exemplary case, we consider the single domain protein par-6 PDZ with and without ligand and allosteric effector...
May 25, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28479334/cdc42-related-genes-are-upregulated-in-helper-t-cells-from-obese-asthmatic-children
#12
Deepa Rastogi, John Nico, Andrew D Johnston, Toni Adrianne M Tobias, Yurydia Jorge, Fernando Macian, John M Greally DMed
BACKGROUND: Pediatric obesity-related asthma is more severe and less responsive to medications than asthma in normal-weight children. Obese asthmatic children have nonatopic TH1-polarized systemic inflammation that correlates with pulmonary function deficits, but the pathways underlying TH1-polarized inflammation are not well understood. OBJECTIVE: We compared the CD4(+) T-cell transcriptome in obese children with asthma with that in normal-weight children with asthma to identify key differentially expressed genes associated with TH1-polarized inflammation...
May 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28478809/aloesin-from-aloe-vera-accelerates-skin-wound-healing-by-modulating-mapk-rho-and-smad-signaling-pathways-in-vitro-and-in-vivo
#13
Hussain Mustatab Wahedi, Minsun Jeong, Jae Kyoung Chae, Seon Gil Do, Hyeokjun Yoon, Sun Yeou Kim
BACKGROUND: Cutaneous wound healing is a complex process involving various regulatory factors at the molecular level. Aloe vera is widely used for cell rejuvenation, wound healing, and skin moisturizing. HYPOTHESIS/PURPOSE: This study aimed to investigate the effects of aloesin from Aloe vera on cutaneous wound healing and mechanisms involved therein. STUDY DESIGN: This study consisted of both in vitro and in vivo experiments involving skin cell lines and mouse model to demonstrate the wound healing effects of aloesin by taking into account several parameters ranging from cultured cell migration to wound healing in mice...
May 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28465339/cdc42-shapes-up-the-epicardium
#14
(no author information available yet)
No abstract text is available yet for this article.
May 1, 2017: Development
https://www.readbyqxmd.com/read/28465335/cdc42-is-required-for-epicardial-and-pro-epicardial-development-by-mediating-fgf-receptor-trafficking-to-the-plasma-membrane
#15
Jingjing Li, Lianjie Miao, Chen Zhao, Wasay Mohiuddin Shaikh Qureshi, David Shieh, Hua Guo, Yangyang Lu, Saiyang Hu, Alice Huang, Lu Zhang, Chen-Leng Cai, Leo Q Wan, Hongbo Xin, Peter Vincent, Harold A Singer, Yi Zheng, Ondine Cleaver, Zhen-Chuan Fan, Mingfu Wu
The epicardium contributes to multiple cardiac lineages and is essential for cardiac development and regeneration. However, the mechanism of epicardium formation is unclear. This study aimed to establish the cellular and molecular mechanisms underlying the dissociation of pro-epicardial cells (PECs) from the pro-epicardium (PE) and their subsequent translocation to the heart to form the epicardium. We used lineage tracing, conditional deletion, mosaic analysis and ligand stimulation in mice to determine that both villous protrusions and floating cysts contribute to PEC translocation to myocardium in a CDC42-dependent manner...
May 1, 2017: Development
https://www.readbyqxmd.com/read/28460460/clinical-relevance-of-the-transcriptional-signature-regulated-by-cdc42-in-colorectal-cancer
#16
Fatima Valdés-Mora, Warwick J Locke, Eva Bandrés, David Gallego-Ortega, Paloma Cejas, Miguel Angel García-Cabezas, Yolanda Colino-Sanguino, Jaime Feliú, Teresa Gómez Del Pulgar, Juan Carlos Lacal
CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28457749/an-fak-yap-mtor-signaling-axis-regulates-stem-cell-based-tissue-renewal-in-mice
#17
Jimmy Kuang-Hsien Hu, Wei Du, Samuel J Shelton, Michael C Oldham, C Michael DiPersio, Ophir D Klein
Tissue homeostasis requires the production of newly differentiated cells from resident adult stem cells. Central to this process is the expansion of undifferentiated intermediates known as transit-amplifying (TA) cells, but how stem cells are triggered to enter this proliferative TA state remains an important open question. Using the continuously growing mouse incisor as a model of stem cell-based tissue renewal, we found that the transcriptional cofactors YAP and TAZ are required both to maintain TA cell proliferation and to inhibit differentiation...
April 18, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28455352/correction-for-xu-et-al-interaction-of-the-small-gtpase-cdc42-with-arginine-kinase-restricts-white-spot-syndrome-virus-in-shrimp
#18
Ji-Dong Xu, Hai-Shan Jiang, Tian-Di Wei, Ke-Yi Zhang, Xian-Wei Wang, Xiao-Fan Zhao, Jin-Xing Wang
No abstract text is available yet for this article.
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28451966/phenotypic-characterisation-of-breast-cancer-the-role-of-cdc42
#19
Eleni Chrysanthou, Kylie L Gorringe, Chitra Joseph, Madeleine Craze, Christopher C Nolan, Maria Diez-Rodriguez, Andrew R Green, Emad A Rakha, Ian O Ellis, Abhik Mukherjee
PURPOSE: The molecular landscape of breast cancer (BC), especially of the Luminal A subtype, remains to be fully delineated. Transcriptomic data show that Luminal A tumours are enriched for aberrant expression of genes in the cell division control 42 homolog (CDC42) pathway. This study aims to investigate the protein expression of CDC42 in BC and assess its clinicopathological significance. METHODS: Expression of CDC42 protein was examined by immunohistochemistry on tissue microarrays in a well-characterised cohort of 895 early-stage (I-IIIa) primary invasive BCs...
April 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28450422/characterization-of-a-dual-rac-cdc42-inhibitor-mbq-167-in-metastatic-cancer
#20
Tessa Humphries-Bickley, Linette Castillo-Pichardo, Eliud Hernandez-O'Farrill, Luis D Borrero-Garcia, Ingrid Forestier-Roman, Yamil Gerena, Manuel Blanco, Michael J Rivera-Robles, José R Rodriguez-Medina, Luis A Cubano, Cornelis P Vlaar, Suranganie Dharmawardhane
The Rho GTPases Rac (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42 homolog) regulate cell functions governing cancer malignancy, including cell polarity, migration, and cell-cycle progression. Accordingly, our recently developed Rac inhibitor EHop-016 (IC50, 1,100 nmol/L) inhibits cancer cell migration and viability and reduces tumor growth, metastasis, and angiogenesis in vivo Herein, we describe MBQ-167, which inhibits Rac and Cdc42 with IC50 values of 103 and 78 nmol/L, respectively, in metastatic breast cancer cells...
May 2017: Molecular Cancer Therapeutics
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