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https://www.readbyqxmd.com/read/29336357/distinctive-roles-of-rac1-and-rab29-in-lrrk2-mediatedmembrane-trafficking-and-neurite-outgrowth
#1
Min Feng, Xin Hu, Na Li, Fan Hu, Fei Chang, Hong-Fei Xu, Yong-Jian Liu
Parkinson's disease (PD) associated leucine-rich repeat kinase 2 (LRRK2) mutants have shown pathogenic effects on variety of subcellular processes.Two small GTPases Rac1 and Rab29 have been indicated as possible downstream effectors participating in LRRK2 signaling but their detail mechanisms remain unclear. In this study, we have used biochemical and cell biology approaches to address whether two GTPases interact with LRRK2 and hence function differently in LRRK2 mediated pathogenesis.Here we show thatRac1 and Rab29 specifically interact with LRRK2with higher affinity for Rab29and with different preference in functional domain binding...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29330095/crosstalk-between-rac1-mediated-actin-regulation-and-ros-production
#2
REVIEW
Alejandro Acevedo, Christian González-Billault
The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound to a cytosolic activator of NOX...
January 9, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29329780/oncogenic-rac1-and-nras-drive-resistance-to-endoplasmic-reticulum-stress-through-mek-erk-signalling
#3
Michael D Bright, Paul A Clarke, Paul Workman, Faith E Davies
Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. The cellular response to ER-stress is controlled by the unfolded protein response (UPR). Small Rho family GTPases are linked to many cell responses including cell growth and apoptosis. In this study, we investigate the function of small GTPases in cell survival under ER-stress. Using siRNA screening we identify that RAC1 promotes cell survival under ER-stress in cells with an oncogenic N92I RAC1 mutation...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29328460/terrein-inhibits-migration-of-human-breast-cancer-cells-via-inhibition-of-the-rho-and-rac-signaling-pathways
#4
Anongnard Kasorn, Fabien Loison, Thaned Kangsamaksin, Suchada Jongrungruangchok, Mathurose Ponglikitmongkol
Breast cancer is the most common cancer in women worldwide. Progression and aggressiveness of breast cancer is usually associated with its migration and invasion abilities. Recently, natural products with potential anticancer activity have become attractive candidates for alternative treatment of cancer. A fungal metabolite, terrein, isolated from the Aspergillus terreus has been revealed to exhibit selective anticancer activity; although this molecule has a variety of biological activities. The inhibitory effect on cell proliferation in hepatoma, keratinocytes, and lung cancer cells was due to cell cycle arrest without induction of apoptosis...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29323050/long-non-coding-rna-nonmmug014387-promotes-schwann-cell-proliferation-after-peripheral-nerve-injury
#5
Bin Pan, Zhong-Ju Shi, Jia-Yin Yan, Jia-He Li, Shi-Qing Feng
Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1 (Cthrc1). Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321004/rcc2-over-expression-in-tumor-cells-alters-apoptosis-and-drug-sensitivity-by-regulating-rac1-activation
#6
Nan Wu, Dong Ren, Su Li, Wenli Ma, Shaoyan Hu, Yan Jin, Sheng Xiao
BACKGROUND: Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. METHODS: Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs...
January 10, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29312635/lrp6-promotes-invasion-and-metastasis-of-colorectal-cancer-through-cytoskeleton-dynamics
#7
Qian Yao, Yu An, Wei Hou, Ya-Nan Cao, Meng-Fei Yao, Ning-Ning Ma, Lin Hou, Hong Zhang, Hai-Jing Liu, Bo Zhang
Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29307615/protein-phosphatase-1b-dephosphorylates-rho-guanine-nucleotide-dissociation-inhibitor-1-and-suppresses-cancer-cell-migration-and-invasion
#8
Hee Jun Cho, Jong-Tae Kim, Seon-Jin Lee, Yo Sep Hwang, Sang Yoon Park, Bo-Yeon Kim, Jiyun Yoo, Kwan Soo Hong, Jeong-Ki Min, Chul-Ho Lee, Jong-Seok Lim, Suk Ran Yoon, Inpyo Choi, Yong-Kyung Choe, Hee Gu Lee
Rho GTPases control a wide range of cellular processes, and their deregulation is associated with promotion of an aggressive and metastatic tumor phenotype in human cancers. Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays a key role in regulating the activity of Rho GTPases. However, the underlying mechanisms are still unclear. In this study, we show that protein phosphatase 1B (PPM1B) interacts with RhoGDI1 and functions as its phosphatase. Ectopic expression of PPM1B results in dephosphorylation of RhoGDI1 and, thereby, abates the activation of RhoA, Rac1 and CDC42 by epidermal growth factor (EGF)...
January 4, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29305692/cd99-at-the-crossroads-of-physiology-and-pathology
#9
REVIEW
Michela Pasello, Maria Cristina Manara, Katia Scotlandi
CD99 is a cell surface protein with unique features and only partly defined mechanisms of action. This molecule is involved in crucial biological processes, including cell adhesion, migration, death, differentiation and diapedesis, and it influences processes associated with inflammation, immune responses and cancer. CD99 is frequently overexpressed in many types of tumors, particularly pediatric tumors including Ewing sarcoma and specific subtypes of leukemia. Engagement of CD99 induces the death of malignant cells through non-conventional mechanisms...
January 6, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29301608/selective-regulation-of-osteoclast-adhesion-and-spreading-by-plc%C3%AE-pkc%C3%AE-pkc%C3%AE-rhoa-rac1-signaling
#10
Jin-Man Kim, Kyunghee Lee, Daewon Jeong
Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin αvβ3 via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading...
January 5, 2018: BMB Reports
https://www.readbyqxmd.com/read/29298445/lps-promotes-vascular-smooth-muscle-cells-proliferation-through-the-tlr4-rac1-akt-signalling-pathway
#11
Qianran Yin, Dehua Jiang, Lei Li, Yu Yang, Pei Wu, Yuanyuan Luo, Rongli Yang, Dongye Li
BACKGROUND/AIMS: Lipopolysaccharide (LPS) is a potent activator of vascular smooth muscle cells (VSMCs) proliferation, but the underlying mechanism remains unknown. In this study, we knocked down Toll-like receptor 4 (TLR4) and Ras-related C3 botulinum toxin substrate 1 (Rac1) expression using small interfering RNA (siRNA) in order to investigate the effects and possible mechanisms of LPS-induced VSMCs proliferation. METHODS: VSMCs proliferation was monitored by 5-ethynyl-2'-deoxyuridine staining, and Rac1 activity was measured via Glutathione S-transferase pull-down assay...
December 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29288926/efhd2-swiprosin-1-regulates-lps-induced-macrophage-recruitment-via-enhancing-actin-polymerization-and-cell-migration
#12
Ye Tu, Lichao Zhang, Lingchang Tong, Yue Wang, Su Zhang, Rongmei Wang, Ling Li, Zhibin Wang
Macrophage motility is vital in innate immunity, which contributes strategically to the defensive inflammation process. During bacterial infection, lipopolysaccharide (LPS) potently activates the migration of macrophages via the NF-κB/iNOS/c-Src signaling pathway. However, the downstream region of c-Src that participates in macrophage migration is unclear. EFhd2, a novel actin bundling protein, was evaluated for its role in LPS-stimulated macrophage migration in this study. We found that LPS stimulated the up-regulation, tyrosine phosphorylation and membrane translocation of EFhd2 in macrophages...
December 27, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29288339/cdk5-contributes-to-huntington-s-disease-learning-and-memory-deficits-via-modulation-of-brain-region-specific-substrates
#13
Elena Alvarez-Periel, Mar Puigdellívol, Verónica Brito, Florian Plattner, James A Bibb, Jordi Alberch, Silvia Ginés
Cognitive deficits are a major hallmark of Huntington's disease (HD) with a great impact on the quality of patient's life. Gaining a better understanding of the molecular mechanisms underlying learning and memory impairments in HD is, therefore, of critical importance. Cdk5 is a proline-directed Ser/Thr kinase involved in the regulation of synaptic plasticity and memory processes that has been associated with several neurodegenerative disorders. In this study, we aim to investigate the role of Cdk5 in learning and memory impairments in HD using a novel animal model that expresses mutant huntingtin (mHtt) and has genetically reduced Cdk5 levels...
December 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29286138/shrna-induced-silencing-of-ras-related-c3-botulinum-toxin-substrate-1-inhibits-the-proliferation-of-colon-cancer-cells-through-upregulation-of-bad-and-downregulation-of-cyclin-d1
#14
You-Sheng Huang, Na Jie, Yi-Xin Zhang, Ke-Jian Zou, Yang Weng
Ras-related C3 botulinum toxin substrate 1 (RAC1) is a member of the Rho family of small GTPases. Recent studies have reported that RAC1 serves an important role in colon cancer cell proliferation. The present study aimed to investigate the effects of RAC1 knockdown on cell proliferation, cell cycle progression and apoptosis of colon cancer cells. Lentivirus‑mediated short hairpin RNA (shRNA) was used to knockdown RAC1 expression in colon cancer cell lines, and cell proliferation, apoptosis, cell cycle progression were evaluated by MTT assays and flow cytometry...
December 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29284148/itraq-based-comparative-proteome-analysis-for-molecular-mechanism-of-defense-against-acute-ammonia-toxicity-in-pacific-white-shrimp-litopenaeus-vannamei
#15
Xia Lu, Sheng Luan, Ping Dai, Xianhong Meng, Baoxiang Cao, Kun Luo, Jie Kong
In the practical farming of Litopenaeus vannamei, the intensive culture system and environmental pollution usually results in a high concentration of ammonia, which brings large detrimental effects to shrimp, such as increasing the susceptibility to pathogens and even causing high mortality. We have revealed that the survival time under acute ammonia stress varied substantially among different families and obtained ammonia-tolerant (LV_T) and ammonia-sensitive (LV_S) families. In order to understand the molecular mechanism of defense against ammonia toxicity in shrimp, we performed iTRAQ LC-MS/MS proteomic analysis between LV_T and LV_S groups of L...
December 25, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29279389/rsk2-drives-cell-motility-by-serine-phosphorylation-of-larg-and-activation-of-rho-gtpases
#16
Geng-Xian Shi, Won Seok Yang, Ling Jin, Michelle L Matter, Joe W Ramos
Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation. RSK2 directly interacts with LARG and nucleotide-bound Rho isoforms, but not Rac1 or Cdc42...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29278662/microrna-335-5p-suppresses-lower-extremity-deep-venous-thrombosis-by-targeted-inhibition-of-pai-1-via-the-tlr4-signaling-pathway
#17
Cui-Xia Bao, Dong-Xia Zhang, Na-Na Wang, Xiang-Kui Zhu, Qi Zhao, Xiao-Lei Sun
OBJECTIVE: This study aims to investigate the effects of microRNA-335-5p (miR-335-5p) on lower-extremity deep vein thrombosis (LEDVT) by targeting PAI-1 through the TLR4 signaling pathway in rat models. METHOD: siRNA, mimic and inhibitor were used for transfection. The miR-335-5p expression was detected by in situ hybridization. CCK-8 assay and flow cytometry were adopted to detect proliferation, cell cycle and apoptosis, respectively. Scratch test and Matrigel-based tube formation assay were used to detect the effect of miR-335-5p on cell migration ability and tube formation ability...
December 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29277502/tiam1-promotes-thyroid-carcinoma-metastasis-by-modulating-emt-via-wnt-%C3%AE-catenin-signaling
#18
Lin Liu, Bo Wu, Haidong Cai, Dan Li, Yushui Ma, Xuchao Zhu, Zhongwei Lv, Youben Fan, Xiaoping Zhang
Aberrant expression of the guanine nucleotide exchange factor Tiam1 is implicated in the invasive phenotype of many cancers. However, its involvement in thyroid carcinoma and downstream molecular events remains largely undefined. Here, we examined the effects of Tiam1 on the invasiveness and metastasis of thyroid carcinoma in vitro and in vivo and explored the underlying mechanisms by investigating the regulation of Tiam1 expression and the downstream pathways affected. Our results showed that Tiam1 knockdown inhibited the migratory and invasive capacity of thyroid cancer cells, suppressed epithelial-mesenchymal transition (EMT), and inhibited Wnt/β-catenin signaling in vitro...
December 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29277177/-effect-of-circular-rna-ubap2-silencing-on-proliferation-and-invasion-of-human-lung-cancer-a549-cells-and-its-mechanism
#19
Yujing Yin, Hui Gao, Jia Guo, Yang Gao
BACKGROUND: It has been proven that circular RNAs (circRNAs) play an important role on the process of many types cancer and circUBAP2 was a cancer-promoting circRNA, however, the role and mechanism in lung cancer was not clear. The aim of this study is to investigate the effects of circUBAP2 on cell proliferation and invasion of human lung cancer A549 cells. METHODS: CCK-8 assay was employed to detect the effect of circUBAP2 sliencing on cell proliferation of A549 cells...
December 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29276218/signal-diversity-of-receptor-for-advanced-glycation-end-products
#20
REVIEW
Masakiyo Sakaguchi, Rie Kinoshita, Endy Widya Putranto, I Made Winarsa Ruma, I Wayan Sumardika, Chen Youyi, Naoko Tomonobu, Ken-Ichi Yamamoto, Hitoshi Murata
The receptor for advanced glycation end products (RAGE) is involved in inflammatory pathogenesis. It functions as a receptor to multiple ligands such as AGEs, HMGB1 and S100 proteins, activating multiple intracellular signaling pathways with each ligand binding. The molecular events by which ligand-activated RAGE controls diverse signaling are not well understood, but some progress was made recently. Accumulating evidence revealed that RAGE has multiple binding partners within the cytoplasm and on the plasma membrane...
December 2017: Acta Medica Okayama
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