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https://www.readbyqxmd.com/read/28100697/the-histone-demethylase-phf8-is-a-molecular-safeguard-of-the-ifn%C3%AE-response
#1
Elena Asensio-Juan, Raquel Fueyo, Stella Pappa, Simona Iacobucci, Carmen Badosa, Sergi Lois, Miriam Balada, Laia Bosch-Presegué, Alex Vaquero, Sara Gutiérrez, Carme Caelles, Carme Gallego, Xavier de la Cruz, Marian A Martínez-Balbás
A precise immune response is essential for cellular homeostasis and animal survival. The paramount importance of its control is reflected by the fact that its non-specific activation leads to inflammatory events that ultimately contribute to the appearance of many chronic diseases. However, the molecular mechanisms preventing non-specific activation and allowing a quick response upon signal activation are not yet fully understood. In this paper we uncover a new function of PHF8 blocking signal independent activation of immune gene promoters...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28098907/synergistic-combination-of-ys-1-and-adriamycin-inhibits-human-renal-cancer-through-erk1-2-signaling-pathway-in%C3%A2-vitro-and-in%C3%A2-vivo
#2
Xiaowen Yu, Qingqing Yang, Sensen Lin, Shengtao Yuan, Li Sun
Adriamycin (ADM) is a principal drug for the treatment of renal cell cancer (RCC). Due to its limited response and high renal and cardiac toxicity, synergistic effects of ADM in combination with other drugs have been widely researched. In this study, we found the combination between YS-1 and ADM, performed higher anticancer activity on 786-O human RCC cells in vitro and in vivo, than that reported on its anti-angiogenesis effect compared with monotherapy of ADM. Our data showed that when combined with ADM, YS-1 promoted the sensitivity of 786-O cells to ADM...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098263/a-lab-on-a-chip-for-monolith-based-preconcentration-and-electrophoresis-separation-of-phosphopeptides
#3
Monica Araya-Farias, Szymon Dziomba, Benjamin Carbonnier, Mohamed Guerrouache, Ichraf Ayed, Nacera Aboud, Myriam Taverna, N Thuy Tran
A microdevice combining online preconcentration and separation of phosphopeptides was developed in a glass microchip. An ethylene glycol methacrylate phosphate (EGMP), acrylamide (AM) and bisacrylamide (BAA) based monolith was synthesized within microchannels through a photo-driven process. Morphological investigations revealed a homogeneous monolithic structure composed of uniform nodules (∼0.8 μm), with a large pore volume (0.62 cm(3) g(-1)) and sufficiently high specific surface area (34.1 m(2) g(-1))...
January 18, 2017: Analyst
https://www.readbyqxmd.com/read/28096188/erk1-2-phosphorylate-gab2-to-promote-a-negative-feedback-loop-that-attenuates-pi3k-akt-signaling
#4
Xiaocui Zhang, Geneviève Lavoie, Antoine Méant, Léo Aubert, Marie Cargnello, André Haman, Trang Hoang, Philippe P Roux
The scaffolding adapter protein Gab2 (Grb2-associated binder) promotes cell proliferation, survival and motility by engaging several signaling pathways downstream of growth factor and cytokine receptors. In particular, Gab2 plays essential roles in mast cells as it is required for PI3K (phosphoinositide 3-kinase) activation in response to Kit and the high-affinity IgE receptor. While the positive role of Gab2 in PI3K signaling is well documented, very little is known about the mechanisms that attenuate its function...
January 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28092672/bpgap1-spatially-integrates-jnk-erk-signaling-crosstalk-in-oncogenesis
#5
T Jiang, C Q Pan, B C Low
Simultaneous hyperactivation of stress-activated protein kinase/c-Jun N-terminal protein kinase (SAPK/JNK) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascades has been reported in carcinogenesis. However, how they are integrated to promote oncogenesis remains unknown. By analyzing breast invasive carcinoma database (The Cancer Genome Altas), we found that the mRNA expression levels of both JNK1 and ERK2 are positively correlated with the mRNA level of EEA1, an endosome associated protein, indicating the potential JNK/ERK crosstalk at endosome...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28062852/a-proteomic-approach-to-identify-endosomal-cargoes-controlling-cancer-invasiveness
#6
Jesica Diaz-Vera, Sarah Palmer, Juan Ramon Hernandez-Fernaud, Emmanuel Dornier, Louise E Mitchell, Iain Macpherson, Joanne Edwards, Sara Zanivan, Jim C Norman
We have previously shown that Rab17 - a small GTPase associated with epithelial polarity - is specifically suppressed by ERK2 signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this are not known. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp-8 is associated with Rab17 at late endosomes...
January 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28060278/nuclear-magnetic-resonance-spectroscopy-for-the-identification-of-multiple-phosphorylations-of-intrinsically-disordered-proteins
#7
Clément Danis, Clément Despres, Luiza M Bessa, Idir Malki, Hamida Merzougui, Isabelle Huvent, Haoling Qi, Guy Lippens, François-Xavier Cantrelle, Robert Schneider, Xavier Hanoulle, Caroline Smet-Nocca, Isabelle Landrieu
Aggregates of the neuronal Tau protein are found inside neurons of Alzheimer's disease patients. Development of the disease is accompanied by increased, abnormal phosphorylation of Tau. In the course of the molecular investigation of Tau functions and dysfunctions in the disease, nuclear magnetic resonance (NMR) spectroscopy is used to identify the multiple phosphorylations of Tau. We present here detailed protocols of recombinant production of Tau in bacteria, with isotopic enrichment for NMR studies. Purification steps that take advantage of Tau's heat stability and high isoelectric point are described...
December 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28058860/liposome-mediated-rna-interference-delivery-against-erk1-and-erk2-does-not-equally-promote-chemosensitivity-in-human-hepatocellular-carcinoma-cell-line-hepg2
#8
Amir Mehdizadeh, Mohammad Hossein Somi, Masoud Darabi, Safar Farajnia, Abolfazl Akbarzadeh, Soheila Montazersaheb, Mehdi Yousefi, Mortaza Bonyadi
BACKGROUND: Extracellular signal-regulated kinase (Erk)1 and Erk2 are central mediators of mitogen-activated protein kinase signaling pathway, which plays a key role in proliferation and chemoresistance of cancer cells. However, the effect of Erk1 and Erk2 in these processes may not be the same. The aim of this study was to investigate differential effect of Erk1 and Erk2 down-regulation on chemoresistance in human hepatocellular carcinoma (HCC) cells. Expression level and relative expression analysis in HepG2 cells were performed using RT-PCR and qRT-PCR, respectively...
January 6, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28053239/microrna-378-reduces-mesangial-hypertrophy-and-kidney-tubular-fibrosis-via-mapk-signaling
#9
Bo Wang, Kevin Yao, Andrea F Wise, Ricky Lau, Hsin-Hui Shen, Greg H Tesch, Sharon D Ricardo
AIMS: To determine the regulatory role of a novel miRNA, miR-378, in the development of fibrosis through repression of the MAPK1 (ERK2) pathway. METHODS: miR-378 and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. miR-378 transfection of proximal tubular epithelial cells, NRK52E, and mesangial cells was assessed with/without endogenous miR-378 knockdown using the locked nucleic acid (LNA) inhibitor...
January 4, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28045574/autophagy-and-krt8-keratin-8-protect-degeneration-of-retinal-pigment-epithelium-under-oxidative-stress
#10
Ahruem Baek, Soojin Yoon, Jean Kim, Yu Mi Baek, Hanna Park, Daehan Lim, Hyewon Chung, Dong-Eun Kim
Contribution of autophagy and regulation of related proteins to the degeneration of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD) remain unknown. We report that upregulation of KRT8 (keratin 8) as well as its phosphorylation are accompanied with autophagy and attenuated with the inhibition of autophagy in RPE cells under oxidative stress. KRT8 appears to have a dual role in RPE pathophysiology. While increased expression of KRT8 following autophagy provides a cytoprotective role in RPE, phosphorylation of KRT8 induces pathologic epithelial-mesenchymal transition (EMT) of RPE cells under oxidative stress, which is mediated by MAPK1/ERK2 (mitogen-activated protein kinase 1) and MAPK3/ERK1...
January 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28034783/cerebellar-insulin-igf-1-signaling-in-diabetic-rats-effects-of-exercise-training
#11
Mariana Eiras Borges, Alessandra Mussi Ribeiro, José Rodrigo Pauli, Luciana Mendonça Arantes, Eliete Luciano, Leandro Pereira de Moura, José Alexandre Curiacos de Almeida Leme, Alessandra Medeiros, Natália Oliveira Bertolini, Clarice Yoshiko Sibuya, Ricardo José Gomes
The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol...
December 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28030988/functional-roles-of-magnesium-binding-to-extracellular-signal-regulated-kinase-2-explored-by-molecular-dynamics-simulations-and-principal-component-analysis
#12
Jianzhong Chen
Molecular dynamics (MD) simulations coupled with principal component (PC) analysis were carried out to study functional roles of Mg(2+) binding to extracellular signal-regulated kinase 2 (ERK2). The results suggest that Mg(2+) binding heavily decreases eigenvalue of the first principal component and totally inhibits motion strength of ERK2, which favors stabilization of ERK2 structure. Binding free energy predictions indicate that Mg(2+) binding produces an important effect on binding ability of ATP to ERK2 and strengthens the ATP binding...
December 28, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28024406/the-effect-of-conformational-flexibility-on-binding-free-energy-estimation-between-kinases-and-their-inhibitors
#13
Mitsugu Araki, Narutoshi Kamiya, Miwa Sato, Masahiko Nakatsui, Takatsugu Hirokawa, Yasushi Okuno
Accurate prediction of binding affinities of drug candidates to their targets remains challenging because of protein flexibility in solution. Conformational flexibility of the ATP-binding site in the CDK2 and ERK2 kinases was identified using molecular dynamics simulations. The binding free energy (ΔG) of twenty-four ATP-competitive inhibitors toward these kinases was assessed using an alchemical free energy perturbation method, MP-CAFEE. However, large calculation errors of 2-3 kcal/mol were observed using this method, where the free energy simulation starts from a single equilibrated conformation...
December 27, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28013489/rsk2-and-its-binding-partners-in-cell-proliferation-transformation-and-cancer-development
#14
REVIEW
Yong-Yeon Cho
RSK2 is a serine/threonine kinase and a member of the p90 ribosomal S6 kinase (p90(RSK); RSKs) family, which regulates cell proliferation and transformation induced by tumor promoters such as epithelial growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate (TPA), and ultraviolet (UV) radiation. RSKs respond to many growth factors, hormones, neurotransmitters and environmental stresses. In signaling cascades, RSK2 is regulated under the control of extracellular signal-regulated kinase 1 (ERK1) and 2 (ERK2) activities and is positioned upstream of transcription and epigenetic factors involved in cell proliferation, cell transformation and cancer development, as well as some kinases that modulate cell cycle progression...
December 24, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28008418/regulation-of-group-i-metabotropic-glutamate-receptors-by-mapk-erk-in-neurons
#15
Li-Min Mao, John Q Wang
Group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes) are regulated by protein kinases. A recent focus is mitogen-activated protein kinases (MAPK). A prototypic subclass of MAPKs, extracellular signal-regulated kinases (ERK), is densely expressed in adult brain postmitotic neurons. This kinase resides in not only the cytoplasm around the nucleus, also the neuronal peripheral structures such as synapses. Recombinant ERK2 binds to C terminal tails of mGluR1a in vitro and native ERK1/2 forms complexes with mGluR1/5 in neurons in vivo...
2016: Journal of Nature and Science
https://www.readbyqxmd.com/read/27995416/synergistic-action-of-cisplatin-and-echistatin-in-mda-mb-231-breast-cancer-cells
#16
Robert Czarnomysy, Arkadiusz Surażyński, Bożena Popławska, Edyta Rysiak, Natalia Pawłowska, Anna Czajkowska, Krzysztof Bielawski, Anna Bielawska
The aim of our study was to determine whether the use of cisplatin in the presence echistatin in MDA-MB-231 breast cancer cells leads to a reduction of toxic effects associated with the use of cisplatin. The expression of β1-integrin and insulin-like growth factor 1 receptor (IGF-IR), signaling pathway protein expression: protein kinase B (AKT), mitogen-activated protein kinases (ERK1/ERK2), nuclear factor kappa B (NFκB), and caspase-3 and -9 activity was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis...
December 19, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27994729/macrocyclic-inhibitors-of-erk2-kinase
#17
EDITORIAL
Gerard Rosse
No abstract text is available yet for this article.
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27975251/the-study-of-posttranslational-modifications-of-tau-protein-by-nuclear-magnetic-resonance-spectroscopy-phosphorylation-of-tau-protein-by-erk2-recombinant-kinase-and-rat-brain-extract-and-acetylation-by-recombinant-creb-binding-protein
#18
Haoling Qi, Clément Despres, Sudhakaran Prabakaran, François-Xavier Cantrelle, Béatrice Chambraud, Jeremy Gunawardena, Guy Lippens, Caroline Smet-Nocca, Isabelle Landrieu
Nuclear magnetic resonance (NMR) spectroscopy can be used as an analytical tool to investigate posttranslational modifications of protein. NMR is a valuable tool to map the interaction regions of protein partners. Here, we present protocols that have been developed in the course of our studies of the neuronal Tau protein. Tau is found aggregated in the neurons of Alzheimer's disease patients. Development of the disease is accompanied by increased, abnormal phosphorylation and acetylation of Tau. We have used NMR to investigate how these posttranslational modifications of Tau affect the interactions with its partners...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27959381/nobiletin-a-citrus-flavonoid-activates-vasodilator-stimulated-phosphoprotein-in-human-platelets-through-non-cyclic-nucleotide-related-mechanisms
#19
Thanasekaran Jayakumar, Kao-Chang Lin, Wan-Jung Lu, Chia-Ying Lin, Geraldine Pitchairaj, Jiun-Yi Li, Joen-Rong Sheu
Nobiletin, a bioactive polymethoxylated flavone, has been described to possess a diversity of biological effects through its antioxidant and anti-inflammatory properties. Vasodilator-stimulated phosphoprotein (VASP) is a common substrate for cyclic AMP and cyclic GMP-regulated protein kinases [i.e., cyclic AMP-dependent protein kinase (PKA; also known as protein kinase A) and cyclic GMP-dependent protein kinase (PKG; also known as protein kinase G)] and it has been shown to be directly phosphorylated by protein kinase C (PKC)...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27941878/the-molecular-mechanisms-underlying-the-er%C3%AE-36-mediated-signaling-in-breast-cancer
#20
S Omarjee, J Jacquemetton, C Poulard, N Rochel, A Dejaegere, Y Chebaro, I Treilleux, E Marangoni, L Corbo, M Le Romancer
Alterations in estrogen-mediated cellular signaling have largely been implicated in the pathogenesis of breast cancer. Here, we investigated the signaling regulation of a splice variant of the estrogen receptor, namely estrogen receptor (ERα-36), associated with a poor prognosis in breast cancers. Coupling in vitro and in vivo approaches we determined the precise sequential molecular events of a new estrogen signaling network in an ERα-negative cell line and in an original patient-derived xenograft. After estrogen treatment, ERα-36 rapidly associates with Src at the level of the plasma membrane, initiating downstream cascades, including MEK1/ERK activation and paxillin phosphorylation on S126, which in turn triggers a higher expression of cyclin D1...
12, 2016: Oncogene
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