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https://www.readbyqxmd.com/read/28733212/the-peroxyl-radical-induced-oxidation-of-escherichia-coli-ftsz-and-its-single-tryptophan-mutant-y222w-modifies-specific-side-chains-generates-protein-cross-links-and-affects-biological-function
#1
Elizabeth Escobar-Álvarez, Fabian Leinisch, Gissela Araya, Octavio Monasterio, Lasse G Lorentzen, Eduardo Silva, Michael J Davies, Camilo López-Alarcón
FtsZ (filamenting temperature-sensitive mutant Z) is a key protein in bacteria cell division. The wild-type Escherichia coli FtsZ sequence (FtsZwt) contains three tyrosine (Tyr, Y) and sixteen methionine (Met, M) residues. The Tyr at position 222 is a key residue for FtsZ polymerization. Mutation of this residue to tryptophan (Trp, W; mutant Y222W) inhibits GTPase activity resulting in an extended time in the polymerized state compared to FtsZwt. Protein oxidation has been highlighted as a determinant process for bacteria resistance and consequently oxidation of FtsZwt and the Y222W mutant, by peroxyl radicals (ROO•) generated from AAPH (2,2'-azobis(2-methylpropionamidine) dihydrochloride) was studied...
July 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28729758/analysis-of-correlated-mutations-in-ras-g-domain
#2
Ekta Pathak
Ras GTPases are most prevalent proto-oncogenes in human cancer. Mutations in Ras remain untreatable more than three decades after the initial discovery. At the amino acid level, some residues under physical or functional constraints exhibit correlated mutations also known as coevolving/covariant residues. Revealing intra-molecular co-evolution between amino acid sites of proteins has become an emerging area of research as it enlightens the importance of variable regions. Here, I have identified and analyzed the coevolving residues in the Ras GTP binding domain (G-domain)...
2017: Bioinformation
https://www.readbyqxmd.com/read/28729736/the-relationship-between-folding-and-activity-in-ureg-an-intrinsically-disordered-enzyme
#3
Marta Palombo, Alessio Bonucci, Emilien Etienne, Stefano Ciurli, Vladimir N Uversky, Bruno Guigliarelli, Valérie Belle, Elisabetta Mileo, Barbara Zambelli
A growing body of literature on intrinsically disordered proteins (IDPs) led scientists to rethink the structure-function paradigm of protein folding. Enzymes are often considered an exception to the rule of intrinsic disorder (ID), believed to require a unique structure for catalysis. However, recent studies revealed the presence of disorder in several functional native enzymes. In the present work, we address the importance of dynamics for catalysis, by investigating the relationship between folding and activity in Sporosarcina pasteurii UreG (SpUreG), a P-loop GTPase and the first discovered native ID enzyme, involved in the maturation of the nickel-containing urease...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729673/distinct-functional-relevance-of-dynamic-gtpase-cysteine-methylation-in-fission-yeast
#4
Alejandro Franco, Teresa Soto, Rebeca Martín-García, Marisa Madrid, Beatriz Vázquez-Marín, Jero Vicente-Soler, Pedro M Coll, Mariano Gacto, Pilar Pérez, José Cansado
The final step in post-translational processing of Ras and Rho GTPases involves methylation of the prenylated cysteine residue by an isoprenylcysteine-O-carboxyl methyltransferase (ICMT). ICMT activity is essential for cell growth and development in higher eukaryotes, and inhibition of GTPase methylation has become an attractive target in cancer therapy to inactivate prenylated oncoproteins. However, the specificity and dynamics of the GTPase methylation process remain to be fully clarified. Notably, cells lacking Mam4, the ICMT ortholog in the fission yeast Schizosaccharomyces pombe, are viable...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726776/autophagosome-maturation-mediated-by-rab7-contributes-to-neuroprotection-of-hypoxic-preconditioning-against-global-cerebral-ischemia-in-rats
#5
Lixuan Zhan, Siyuan Chen, Kongping Li, Donghai Liang, Xinyong Zhu, Liu Liu, Zhiwei Lu, Weiwen Sun, En Xu
Autophagy disruption leads to neuronal damage in hypoxic-ischemic brain injury. Rab7, a member of the Rab GTPase superfamily, has a unique role in the regulation of autophagy. Hypoxic preconditioning (HPC) provides neuroprotection against transient global cerebral ischemia (tGCI). However, the underlying mechanisms remain poorly understood. Thus, the current study explored the potential molecular mechanism of the neuroprotective effect of HPC by investigating how Rab7 mediates autophagosome (AP) maturation after tGCI in adult rats...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726720/tgf-%C3%AE-dependent-growth-arrest-and-cell-migration-in-benign-and-malignant-breast-epithelial-cells-are-antagonistically-controlled-by-rac1-and-rac1b
#6
Catharina Melzer, Juliane von der Ohe, Ralf Hass, Hendrik Ungefroren
Despite improvements in diagnosis and treatment, breast cancer is still the most common cancer type among non-smoking females. TGF-β can inhibit breast cancer development by inducing cell cycle arrest in both, cancer cells and, as part of a senescence program in normal human mammary epithelial cells (HMEC). Moreover, TGF-β also drives cell migration and invasion, in part through the small GTPases Rac1 and Rac1b. Depletion of Rac1b or Rac1 and Rac1b in MDA-MB-231 or MDA-MB-435s breast cancer cells by RNA interference enhanced or suppressed, respectively, TGF-β1-induced migration/invasion...
July 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28726538/marked-bleeding-diathesis-in-patients-with-platelet-dysfunction-due-to-a-novel-mutation-in-rasgrp2-encoding-caldag-gefi-p-gly305asp
#7
Emilse Bermejo, Maria F Alberto, David S Paul, Aaron A Cook, Paquita Nurden, Analia Sanchez Luceros, Alan T Nurden, Wolfgang Bergmeier
Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#8
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724429/the-noncoding-rna-hoxd-as1-is-a-critical-regulator-of-the-metastasis-and-apoptosis-phenotype-in-human-hepatocellular-carcinoma
#9
Shan Lu, Jiansheng Zhou, Yimin Sun, Nan Li, Mingyong Miao, Binghua Jiao, Huan Chen
BACKGROUND: Despite accumulating evidence that long noncoding RNAs (lncRNAs) are associated with cancer development in multiple types of cancer, the biological roles of many lncRNAs in human hepatocellular carcinoma (HCC) metastasis have not been well characterized. METHODS: A lncRNA+ mRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in metastatic HCC tissues compared to non-metastatic tissue. RESULTS: We observed remarkable overexpression of HOXD-AS1 in metastatic cancer tissues...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28720901/a-novel-connection-between-the-cell-wall-integrity-and-the-pka-pathways-regulates-cell-wall-stress-response-in-yeast
#10
Raúl García, Enrique Bravo, Sonia Diez-Muñiz, Cesar Nombela, Jose M Rodríguez-Peña, Javier Arroyo
Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway, and a broad group of genes regulated independently of Slt2. Genes negatively regulated by the cyclic AMP/Protein Kinase A (PKA) signaling pathway were overrepresented in the latter group...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720784/snap-tagged-chikungunya-virus-replicons-improve-visualisation-of-non-structural-protein-3-by-fluorescence-microscopy
#11
Roland Remenyi, Grace C Roberts, Carsten Zothner, Andres Merits, Mark Harris
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs)...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720584/protein-kinase-n2-regulates-amp-kinase-signaling-and-insulin-responsiveness-of-glucose-metabolism-in-skeletal-muscle
#12
Maxwell A Ruby, Isabelle Riedl, Julie Massart, Marcus Åhlin, Juleen R Zierath
Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. As skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. While Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo...
July 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28720574/fructose-1-6-bisphosphatase-inhibits-erk-activation-and-bypasses-gemcitabine-resistance-in-pancreatic-cancer-by-blocking-iqgap1-mapk-interaction
#13
Xin Jin, Yunqian Pan, Liguo Wang, Tao Ma, Lizhi Zhang, Amy H Tang, Daniel D Billadeau, Heshui Wu, Haojie Huang
Dysregulation of the mitogen-activated protein kinase (MAPK) pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and extracellular signaling-regulated kinases (ERK). Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here we demonstrate that FBP1 acts as a negative modulator of the IQGAP1-MAPK signaling axis in PDAC cells...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716909/internalized-cd44s-splice-isoform-attenuates-egfr-degradation-by-targeting-rab7a
#14
Wei Wang, Honghong Zhang, Sali Liu, Chung Kwon Kim, Yilin Xu, Lisa A Hurley, Ryo Nishikawa, Motoo Nagane, Bo Hu, Alexander H Stegh, Shi-Yuan Cheng, Chonghui Cheng
CD44 has been postulated as a cell surface coreceptor for augmenting receptor tyrosine kinase (RTK) signaling. However, how exactly CD44 triggers RTK-dependent signaling remained largely unclear. Here we report an unexpected mechanism by which the CD44s splice isoform is internalized into endosomes to attenuate EGFR degradation. We identify a CD44s-interacting small GTPase, Rab7A, and show that CD44s inhibits Rab7A-mediated EGFR trafficking to lysosomes and subsequent degradation. Importantly, CD44s levels correlate with EGFR signature and predict poor prognosis in glioblastomas...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28712859/tyr42-phosphorylation-of-rhoa-gtpase-promotes-tumorigenesis-through-nuclear-factor-nf-%C3%AE%C2%BAb
#15
Jae-Gyu Kim, Kyoung-Chan Choi, Chang-Won Hong, Hwee-Seon Park, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Bong Park
Dysregulation of reactive oxygen species (ROS) levels is implicated in the pathogenesis of several diseases, including cancer. However, the molecular mechanisms of ROS in tumorigenesis have not been clearly elucidated. Hydrogen peroxide activated nuclear factor-κB (NF-κB) and RhoA GTPase. In particular, we found that hydrogen peroxide phosphorylated RhoA at Tyr42 via Src. P-Ty42 residue of RhoA was a binding site of Vav2, a guanine nucleotide exchange factor (GEF) that activates p-Tyr42 RhoA. P-Tyr42 RhoA then bound to IκB kinase γ (IKKγ), leading IKKβ activation...
July 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28710770/an-arabidopsis-kinase-cascade-influences-auxin-responsive-cell-expansion
#16
Tara A Enders, Elizabeth M Frick, Lucia C Strader
Mitogen-activated protein kinase (MPK) cascades are conserved mechanisms of signal transduction across eukaryotes. Despite the importance of MPK proteins in signaling events, specific roles for many Arabidopsis MPK proteins remain unknown. Multiple studies have suggested roles for MPK signaling in a variety of auxin-related processes. To identify MPK proteins with roles in auxin response, we screened mpk insertional alleles and identified mpk1-1 as a mutant that displays hypersensitivity in auxin-responsive cell expansion assays...
July 15, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28710431/hiv-1-enhances-mtorc1-activity-and-repositions-lysosomes-to-the-periphery-by-co-opting-rag-gtpases
#17
Alessandro Cinti, Valerie Le Sage, Miroslav P Milev, Fernando Valiente-Echeverría, Christina Crossie, Marie-Joelle Miron, Nelly Panté, Martin Olivier, Andrew J Mouland
HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endosome/lysosome (LEL) trafficking in stressful conditions. First, HIV-1 enhances the activity of the master regulator of protein synthesis, the mammalian target of rapamycin (mTOR). Second, the virus commandeers mTOR-associated late endosome/lysosome (LEL) trafficking and counteracts metabolic and environmental stress-induced intracellular repositioning of LEL...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710284/the-neuronal-protein-neurexin-directly-interacts-with-the-scribble-pix-complex-to-stimulate-f-actin-assembly-for-synaptic-vesicle-clustering
#18
Menglong Rui, Jinjun Qian, Lijuan Liu, Yihan Cai, Huihui Lv, Junhai Han, Zhengping Jia, Wei Xie
Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neuro-transmission. However, how SV cluster in particular synaptic compartments to maintain normal neurotransmitter release remains a mystery. The presynaptic protein Neurexin (NRX) plays a significant role in synaptic architecture and function, and some evidences suggest that NRX is associated with neurological disorders, including autism spectrum disorders. However, the role of NRX in SV clustering is unclear...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28709956/activation-of-human-gonadotropin-releasing-hormone-receptor-promotes-down-regulation-of-arhgap18-and-regulates-the-cell-invasion-of-mda-mb-231%C3%A2-cells
#19
Arturo Aguilar-Rojas, Guadalupe Maya-Núñez, Maira Huerta-Reyes, Marco Allán Pérez-Solis, Raúl Silva-García, Nancy Guillén, Jean-Christophe Olivo-Marin
The Gonadotropin-Releasing Hormone Receptor (GnRHR) is expressed mainly in the gonadotrope membrane of the adenohypophysis and its natural ligand, the Gonadotropin-Releasing Hormone (GnRH), is produced in anterior hypothalamus. Furthermore, both molecules are also present in the membrane of cells derived from other reproductive tissues such as the breast, endometrium, ovary, and prostate, as well as in tumors derived from these tissues. The functions of GnRH receptor and its hormone in malignant cells have been related with the decrease of proliferation and the invasiveness of those tumors however, little is known about the molecules associated with the signaling pathways regulated by both molecules in malignant cells...
July 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28709747/interaction-of-the-innate-immune-system-with-positive-strand-rna-virus-replication-organelles
#20
Enzo Maxim Scutigliani, Marjolein Kikkert
The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines...
June 27, 2017: Cytokine & Growth Factor Reviews
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