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https://www.readbyqxmd.com/read/29776664/rhod-localization-and-function-is-dependent-on-its-gtp-gdp-bound-state-and-unique-n-terminal-motif
#1
Magdalena Blom, Katarina Reis, Pontus Aspenström
The atypical Rho GTPase RhoD has previously been shown to have a major impact on the organization and function of the actin filament system. However, when first discovered, RhoD was found to regulate endosome trafficking and dynamics and we therefore sought to investigate this regulation in more detail. We found that exogenously expressed RhoD in human fibroblasts localized to vesicles and the plasma membrane and that the active GTP-bound conformation was required for the plasma membrane localization but not for vesicle localization...
May 16, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29773903/circadian-regulator-nr1d2-regulates-glioblastoma-cell-proliferation-and-motility
#2
Min Yu, Wenjing Li, Qianqian Wang, Yan Wang, Fei Lu
Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773874/mutations-in-six-nephrosis-genes-delineate-a-pathogenic-pathway-amenable-to-treatment
#3
Shazia Ashraf, Hiroki Kudo, Jia Rao, Atsuo Kikuchi, Eugen Widmeier, Jennifer A Lawson, Weizhen Tan, Tobias Hermle, Jillian K Warejko, Shirlee Shril, Merlin Airik, Tilman Jobst-Schwan, Svjetlana Lovric, Daniela A Braun, Heon Yung Gee, David Schapiro, Amar J Majmundar, Carolin E Sadowski, Werner L Pabst, Ankana Daga, Amelie T van der Ven, Johanna M Schmidt, Boon Chuan Low, Anjali Bansal Gupta, Brajendra K Tripathi, Jenny Wong, Kirk Campbell, Kay Metcalfe, Denny Schanze, Tetsuya Niihori, Hiroshi Kaito, Kandai Nozu, Hiroyasu Tsukaguchi, Ryojiro Tanaka, Kiyoshi Hamahira, Yasuko Kobayashi, Takumi Takizawa, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Naonori Kumagai, Kazumoto Iijima, Henry Fehrenbach, Jameela A Kari, Sherif El Desoky, Sawsan Jalalah, Radovan Bogdanovic, Nataša Stajić, Hildegard Zappel, Assel Rakhmetova, Sharon-Rose Wassmer, Therese Jungraithmayr, Juergen Strehlau, Aravind Selvin Kumar, Arvind Bagga, Neveen A Soliman, Shrikant M Mane, Lewis Kaufman, Douglas R Lowy, Mohamad A Jairajpuri, Richard P Lifton, York Pei, Martin Zenker, Shigeo Kure, Friedhelm Hildebrandt
No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29765517/targeting-the-mevalonate-pathway-is-a-novel-therapeutic-approach-to-inhibit-oncogenic-foxm1-transcription-factor-in-human-hepatocellular-carcinoma
#4
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Hidetoshi Eguchi, Hisakazu Ogita, Yuichiro Doki, Masaki Mori, Tomohide Tatsumi, Tetsuo Takehara
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764867/3d-fibrin-stiffness-mediates-dormancy-of-tumor-repopulating-cells-via-a-cdc42-driven-tet2-epigenetic-program
#5
Yuying Liu, Jiadi Lv, Xiaoyu Liang, Xiaonan Yin, Le Zhang, Degao Chen, Xun Jin, Roland Fiskesund, Ke Tang, Jingwei Ma, Huafeng Zhang, Wenqian Dong, Siqi Mo, Tianzhen Zhang, Feiran Cheng, Yabo Zhou, Jing Xie, Ning Wang, Bo Huang
Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating cells (TRC) sense mechanical signals and rapidly proliferate in a 90 Pa soft fibrin matrix. Here we show that a stiff mechanical environment induces TRC dormancy via an epigenetic program initiated by translocation of Cdc42, a cytosolic regulator of mechanotransduction, into the nucleus, where it promotes transcription of hydroxymethylating enzyme Tet2...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29760342/1-2-3-triazolyl-ester-of-ketorolac-15k-boosting-both-heat-endurance-and-lifespan-of-c-elegans-by-down-regulating-pak1-at-nm-levels
#6
Binh C Nguyen, Sung-A Kim, Seong-Min Won, Sang-Kyu Park, Yoshihiro Uto, Hiroshi Maruta
PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic/ageing kinase, and its dysfunction extends the healthy lifespan of C. elegans by activating HSP16 gene. 15K is a highly cell-permeable 1,2,3-triazolyl ester of ketorolac that down-regulates both PAK1 and its down-stream COX-2 in R- and S-forms, respectively. 15K is 500-5,000 times more potent than ketorolac, an old pain-killer, inhibiting the growth of cancer cell lines with IC50 ranging 5-24 nM. Scores of natural and synthetic PAK1-blockers have been shown to extend the lifespan of small animals such as C...
2018: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/29755292/decoding-common-features-of-neurodegenerative-disorders-from-differentially-expressed-genes-to-pathways
#7
Rabia Habib, Nighat Noureen, Neha Nadeem
Background: Neurodegeneration is a progressive/irreversible loss of neurons, building blocks of our nervous system. Their degeneration gradually collapses the entire structural and functional system manifesting in myriads of clinical disorders categorized as Neurodegenerative Disorders (NDs) such as Alzheimer's Disease, (AD), Parkinson's Disease (PD), Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). NDs are characterized by a puzzling interplay of molecular and cellular defects affecting subset of neuronal populations in specific affected brain areas...
May 2018: Current Genomics
https://www.readbyqxmd.com/read/29746010/rho-kinase-rock-collaborates-with-pak-to-regulate-actin-polymerization-and-contraction-in-airway-smooth-muscle
#8
Wenwu Zhang, Bhupal P Bhetwal, Susan J Gunst
KEY POINTS: The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29745557/-effects-of-silencing-snail1-gene-on-the-expression-of-tight-junction-proteins-and-the-migration-ability-of-hep-2-cells
#9
Shuangfeng Liu, Yang Shen, Tang Feng, Xiaoheng Liu
To investigate the effects of Snail1 gene silence on the expression of tight junction proteins and the migration ability of Hep-2 cells, Hep-2 cells were transfected with plasmids which is containing the shRNA of Snail1 gene, and cultured till the cells could be passaged stably (named Sh-snail1 cells). The expression of tight junction proteins (ZO-1, Occludin, Claudin-5) were detected by Western blot. The migration ability of Sh-snail1 cells was investigated by wound healing assay, and the protein expression of members of RhoGTPase family (RhoA, Cdc42) was detected by Western blot, which is closely related to the migration ability...
August 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
https://www.readbyqxmd.com/read/29743604/small-gtpases-and-bar-domain-proteins-regulate-branched-actin-polymerisation-for-clathrin-and-dynamin-independent-endocytosis
#10
Mugdha Sathe, Gayatri Muthukrishnan, James Rae, Andrea Disanza, Mukund Thattai, Giorgio Scita, Robert G Parton, Satyajit Mayor
Using real-time TIRF microscopy imaging, we identify sites of clathrin and dynamin-independent CLIC/GEEC (CG) endocytic vesicle formation. This allows spatio-temporal localisation of known molecules affecting CG endocytosis; GBF1 (a GEF for ARF1), ARF1 and CDC42 which appear sequentially over 60 s, preceding scission. In an RNAi screen for BAR domain proteins affecting CG endocytosis, IRSp53 and PICK1, known interactors of CDC42 and ARF1, respectively, were selected. Removal of IRSp53, a negative curvature sensing protein, abolishes CG endocytosis...
May 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29737580/long-non-coding-rna-foxd2-as1-contributes-to-colorectal-cancer-proliferation-through-its-interaction-with-microrna-185-5p
#11
Yanyan Zhu, Liang Qiao, Yun Zhou, Ning Ma, Chaojie Wang, Jianwei Zhou
Emerging evidence has indicated that long non-coding RNA plays an important role in the carcinogenesis at the transcriptional and post-translational levels. The regulation of carcinogenesis related effectors is potent in the determination of tumor initiation and progression. In current study, FOXD2-AS1 was found to interact with miR-185-5p to modulate proliferation, migration and invasion of colorectal cancer (CRC) cells. Interestingly, cell division control (CDC) 42 expression was significantly influenced by FOXD2-AS1 and miR-185-5p...
May 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29734338/rit1-controls-actin-dynamics-via-complex-formation-with-rac1-cdc42-and-pak1
#12
Uta Meyer Zum Büschenfelde, Laura Isabel Brandenstein, Leonie von Elsner, Kristina Flato, Tess Holling, Martin Zenker, Georg Rosenberger, Kerstin Kutsche
RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1...
May 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29718000/structure-of-the-tandem-px-ph-domains-of-bem3-from-saccharomyces-cerevisiae
#13
Imtiaz Ali, Sungmin Eu, Daniel Koch, Nathalie Bleimling, Roger S Goody, Matthias P Müller
The structure of the tandem lipid-binding PX and pleckstrin-homology (PH) domains of the Cdc42 GTPase-activating protein Bem3 from Saccharomyces cerevisiae (strain S288c) has been determined to a resolution of 2.2 Å (Rwork = 21.1%, Rfree = 23.4%). It shows that the domains adopt a relative orientation that enables them to simultaneously bind to a membrane and suggests possible cooperativity in membrane binding.
May 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/29709479/modulation-of-angiopoietin-2-release-from-endothelial-cells-and-angiogenesis-by-the-synaptic-protein-neuroligin-2
#14
Margherita Pergolizzi, Laura Bizzozero, Elena Riccitelli, Davide Pascal, Anna Valeria Samarelli, Federico Bussolino, Marco Arese
The synaptic protein Neuroligin 2, similarly to its isoform Neuroligin 1, is produced by endothelial cells, but its activity in the vascular context remains unknown. This study aimed at verifying the hypothesis that Neuroligin 2, in parallel with its extraneuronal involvement in pancreatic beta cells exocytosis, modulated cytokine release from endothelial cells and consequently angiogenesis. We used in vitro approaches to modulate Neuroligin 2 expression and Neuroligin 2 null mice to test our hypotheses. In vitro, upon VEGF stimulation, Neuroligin 2 silencing strongly reduces Angiopoietin 2 release in the medium and increases the endothelial cell retention of Weibel Palade Bodies, the specialized organelles that store Angiopoietin 2 and various other cytokines...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29706346/an-osteoporosis-risk-snp-at-1p36-12-acts-as-an-allele-specific-enhancer-to-modulate-linc00339-expression-via-long-range-loop-formation
#15
Xiao-Feng Chen, Dong-Li Zhu, Man Yang, Wei-Xin Hu, Yuan-Yuan Duan, Bing-Jie Lu, Yu Rong, Shan-Shan Dong, Ruo-Han Hao, Jia-Bin Chen, Yi-Xiao Chen, Shi Yao, Hlaing Nwe Thynn, Yan Guo, Tie-Lin Yang
Genome-wide association studies (GWASs) have reproducibly associated variants within intergenic regions of 1p36.12 locus with osteoporosis, but the functional roles underlying these noncoding variants are unknown. Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339) (∼360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region...
April 14, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29700579/a-cdc42-homolog-in-colletotrichum-gloeosporioides-regulates-morphological-development-and-is-required-for-ros-mediated-plant-infection
#16
Xiaolian Wang, Xin Xu, Yingmei Liang, Yonglin Wang, Chengming Tian
The Rho GTPase Cdc42 is conserved in fungi and plays a key role in regulating polarity establishment, morphogenesis and differentiation. In this study, we identified an ortholog of Cdc42, CgCdc42, and functionally characterized it to determine the role of Cdc42 in the development and pathogenicity of Colletotrichum gloeosporioides, a causal agent of poplar anthracnose. Targeted deletion of CgCdc42 resulted in reduced vegetative growth and dramatic morphological defects, including the formation of elongated conidia and abnormally shaped appressoria...
April 26, 2018: Current Genetics
https://www.readbyqxmd.com/read/29700112/rhoa-rac1-and-cdc42-differentially-regulate-asma-and-collagen-i-expression-in-mesenchymal-stem-cells
#17
Jianfeng Ge, Laurent Burnier, Maria Adamopoulou, Mei Qi Kwa, Matthias Schaks, Klemens Rottner, Cord Brakebusch
Mesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGFβ-induced myofibroblast differentiation of MSC, we generated a novel MSC line and descendants of it lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGFβ-induced expression of αSMA, but not of collagen I α1 (col1a1). While loss of RhoA and Cdc42 reduced αSMA expression, ablation of the Rac1 gene had the opposite effect...
April 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29695291/dna-topoisomerase-ii%C3%AE-stimulates-neurite-outgrowth-in-neural-differentiated-human-mesenchymal-stem-cells-through-regulation-of-rho-gtpases-rhoa-rock2-pathway-and-nurr1-expression
#18
Merve Zaim, Sevim Isik
BACKGROUND: DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases...
April 25, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29694880/modeling-the-dynamics-of-cdc42-oscillation-in-fission-yeast
#19
Bin Xu, Alexandra Jilkine
No abstract text is available yet for this article.
April 24, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29684584/deletion-of-epithelial-cell-specific-cdc42-leads-to-enamel-hypermaturation-in-a-conditional-knockout-mouse-model
#20
Zhihui Tian, Xiaolin Lv, Min Zhang, Xueer Wang, Yinghua Chen, Pei Tang, Pengcheng Xu, Lu Zhang, Buling Wu, Lin Zhang
Recent evidence suggests that GTPases Rho family plays an important role in tooth development; however, the role of Cdc42 in tooth development remains unclear. We aimed to investigate the function of Cdc42 in tooth development and amelogenesis. We generated an epithelial cell-specific K5-Cdc42 knockout (KO) mouse to evaluate post-eruption dental phenotypes using a K5-Cre driver line. This model overcomes the previously reported perinatal lethality. Tooth phenotypes were analyzed by micro X-ray, micro-computed tomography (CT), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), wear rate, shear strength, and a microhardness test...
April 20, 2018: Biochimica et Biophysica Acta
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