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https://www.readbyqxmd.com/read/27889231/nimbolide-inhibits-androgen-independent-prostate-cancer-cells-survival-and-proliferation-by-modulating-multiple-pro-survival-signaling-pathways
#1
P Raja Singh, E Sugantha Priya, S Balakrishnan, R Arunkumar, G Sharmila, M Rajalakshmi, J Arunakaran
BACKGROUND: Prostate cancer is the most prominent cancer in men, experiencing a relapse in disease often express high serum TNF-α levels. It has been correlated with increased cell survival and proliferation of prostate cancer cells. Previous studies reported that nimbolide, a terpenoid derived from the leaves and flowers of neem tree inhibits cancer growth through selective modulation of cell signaling pathways linked to inflammation, survival, proliferation, angiogenesis and metastasis...
November 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27887869/a-highly-diverse-and-functional-na%C3%A3-ve-ubiquitin-variant-library-for-generation-of-intracellular-affinity-reagents
#2
Isabel Leung, Nick Jarvik, Sachdev S Sidhu
We report the design, construction, and validation of a highly diverse phage-displayed naïve ubiquitin variant (Ubv) library. We first conducted a mutation tolerance scan of 27 residues and confirmed that 24 of these could be substituted by chemically diverse amino acids without compromising the display of Ubvs on phage. Subsequently, we constructed a library containing 6.8×10(10) unique members, in which these 24 positions were diversified with a degenerate codon that encodes for 6 aa that are prevalent in protein interaction sites...
November 22, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27861634/molecular-characterization-of-striated-muscle-specific-gab1-isoform-as-a-critical-signal-transducer-for-neuregulin-1-erbb-signaling-in-cardiomyocytes
#3
Taku Yasui, Takeshi Masaki, Yoh Arita, Tomohiko Ishibashi, Tadakatsu Inagaki, Makoto Okazawa, Toru Oka, Wataru Shioyama, Keiko Yamauchi-Takihara, Issei Komuro, Yasushi Sakata, Yoshikazu Nakaoka
Grb2-associated binder (Gab) docking proteins regulate signals downstream of a variety of growth factors and receptor tyrosine kinases. Neuregulin-1 (NRG-1), a member of epidermal growth factor family, plays a critical role for cardiomyocyte proliferation and prevention of heart failure via ErbB receptors. We previously reported that Gab1 and Gab2 in the myocardium are essential for maintenance of myocardial function in the postnatal heart via transmission of NRG-1/ErbB-signaling through analysis of Gab1/Gab2 cardiomyocyte-specific double knockout mice...
2016: PloS One
https://www.readbyqxmd.com/read/27845161/downregulation-of-autophagy-gene-expression-in-endometria-from-women-with-polycystic-ovary-syndrome
#4
Mirjana Sumarac-Dumanovic, Milica Apostolovic, Kristina Janjetovic, Danka Jeremic, Dusan Popadic, Aleksandar Ljubic, Jelena Micic, Jelena Dukanac-Stamenkovic, Aleksandra Tubic, Darko Stevanovic, Dragan Micic, Vladimir Trajkovic
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium...
November 11, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27813071/what-goes-up-must-come-down-a-tripartite-dok-3-grb2-ship1-inhibitory-module-limits-bcr-signaling
#5
Michael Reth, Michael R Gold
Properly regulated immunity requires precise integration of activating and inhibitory signals. As for other lymphocytes, B cells express an antigen-specific activating receptor, the B-cell antigen receptor (BCR), and inhibitory receptors (e.g. FcγRIIb) that exercise checkpoint control on B-cell activation. Moreover, following BCR engagement, CD19 recruits proteins that amplify BCR signaling, while CD22 initiates a negative feedback loop by recruiting proteins that inhibit BCR signaling. Initial BCR signaling is mediated by protein tyrosine kinases and lipid kinases; inhibitory receptors directly antagonize the actions of these enzymes by recruiting protein tyrosine phosphatases and lipid phosphatases and positioning them close to actively signaling BCRs...
November 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27802291/actb-cdkn1b-gapdh-grb2-rhoa-and-sdcbp-were-identified-as-reference-genes-in-neuroendocrine-lung-cancer-via-the-ncounter-technology
#6
Robert Fred Henry Walter, Robert Werner, Claudia Vollbrecht, Thomas Hager, Elena Flom, Daniel Christian Christoph, Jan Schmeller, Kurt Werner Schmid, Jeremias Wohlschlaeger, Fabian Dominik Mairinger
BACKGROUND: Neuroendocrine lung cancer (NELC) represents 25% of all lung cancer cases and large patient collectives exist as formalin-fixed, paraffin-embedded (FFPE) tissue only. FFPE is controversially discussed as source for molecular biological analyses and reference genes for NELC are poorly establishes. MATERIAL AND METHODS: Forty-three representative FFPE-specimens were used for mRNA expression analysis using the digital nCounter technology (NanoString). Based on recent literature, a total of 91 mRNA targets were investigated as potential tumor markers or reference genes...
2016: PloS One
https://www.readbyqxmd.com/read/27793798/epithelial-disruption-of-gab1-perturbs-surfactant-homeostasis-and-predisposes-mice-to-lung-injuries
#7
Kai Wang, Shenlu Qin, Zuyu Liang, Yun Zhang, Yingchun Xu, An Chen, Xiaohong Guo, Hongqiang Cheng, Xue Zhang, Yuehai Ke
GRB2-associated-binding protein 1 (Gab1) belongs to Gab adaptor family (Gabs), which integrates multiple signals in response to the epithelial growth factors. Recent genetic studies identified genetic variants of human Gab1 gene as potential risk factors of asthmatic inflammation. However, Gab1 functions in lungs remain largely unknown. Alveolar type-II cells (AT-IIs) are responsible for surfactant homeostasis, and essentially regulate lung inflammation following various injuries. Here, in vitro knockdown of Gab1 was shown to cause a decrease in surfactant proteins (SPs) in AT-IIs...
October 28, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27790245/associations-of-mrna-microrna-for-the-shared-downstream-molecules-of-egfr-and-alternative-tyrosine-kinase-receptors-in-non-small-cell-lung-cancer
#8
Fengfeng Wang, Fei Meng, Lili Wang, S C Cesar Wong, William C S Cho, Lawrence W C Chan
Lung cancer is the top cancer killer worldwide with high mortality rate. Majority belong to non-small cell lung cancers (NSCLCs). The epidermal growth factor receptor (EGFR) has been broadly explored as a drug target for therapy. However, the drug responses are not durable due to the acquired resistance. MicroRNAs (miRNAs) are small non-coding and endogenous molecules that can inhibit mRNA translation initiation and degrade mRNAs. We wonder if some downstream molecules shared by EGFR and the other tyrosine kinase receptors (TKRs) further transduce the signals alternatively, and some miRNAs play the key roles in affecting the expression of these downstream molecules...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27780040/functional-coordination-of-wave-and-wasp-in-c-%C3%A2-elegans-neuroblast-migration
#9
Zhiwen Zhu, Yongping Chai, Yuxiang Jiang, Wenjing Li, Huifang Hu, Wei Li, Jia-Wei Wu, Zhi-Xin Wang, Shanjin Huang, Guangshuo Ou
Directional cell migration is critical for metazoan development. We define two molecular pathways that activate the Arp2/3 complex during neuroblast migration in Caenorhabditis elegans. The transmembrane protein MIG-13/Lrp12 is linked to the Arp2/3 nucleation-promoting factors WAVE or WASP through direct interactions with ABL-1 or SEM-5/Grb2, respectively. WAVE mutations partially impaired F-actin organization and decelerated cell migration, and WASP mutations did not inhibit cell migration but enhanced migration defects in WAVE-deficient cells...
October 24, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27779214/disabled-2-determines-commitment-of-a-pre-adipocyte-population-in-juvenile-mice
#10
Wensi Tao, Robert Moore, Yue Meng, Toni M Yeasky, Elizabeth R Smith, Xiang-Xi Xu
Disabled-2 (Dab2) is a widely expressed clathrin binding endocytic adaptor protein and known for the endocytosis of the low-density lipoprotein (LDL) family receptors. Dab2 also modulates endosomal Ras/MAPK (Erk1/2) activity by regulating the disassembly of Grb2/Sos1 complexes associated with clathrin-coated vesicles. We found that the most prominent phenotype of Dab2 knockout mice was their striking lean body composition under a high fat and high caloric diet, although the weight of the mutant mice was indistinguishable from wild-type littermates on a regular chow...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27699085/proteomic-analysis-of-the-peri-infarct-area-after-human-umbilical-cord-mesenchymal-stem-cell-transplantation-in-experimental-stroke
#11
He Dongsheng, Zhang Zhuo, Lao Jiamin, Meng Hailan, Han Lijuan, Chen Fan, Ye Dan, Zhang He, Xu Yun
Among various therapeutic approaches for stroke, treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) has acquired some promising results. However, the underlying mechanisms remain unclear. We analyzed the protein expression spectrum of the cortical peri-infarction region after ischemic stroke followed by treatment with hUC-MSCs, and found 16 proteins expressed differentially between groups treated with or without hUC-MSCs. These proteins were further determined by Gene Ontology term analysis and network with CD200-CD200R1, CCL21-CXCR3 and transcription factors...
October 2016: Aging and Disease
https://www.readbyqxmd.com/read/27666924/integrated-microrna-and-protein-expression-analysis-reveals-novel-microrna-regulation-of-targets-in-fetal-down-syndrome
#12
Hua Lin, Weiguo Sui, Wuxian Li, Qiupei Tan, Jiejing Chen, Xiuhua Lin, Hui Guo, Minglin Ou, Wen Xue, Ruohan Zhang, Yong Dai
Down syndrome (DS) is caused by trisomy of human chromosome 21 and is associated with a number of deleterious phenotypes. To investigate the role of microRNA (miRNA) in the regulation of DS, high‑throughput Illumina sequencing technology and isobaric tagging for relative and absolute protein quantification analysis were utilized for simultaneous expression profiling of miRNA and protein in fetuses with DS and normal fetuses. A total of 344 miRNAs were associated with DS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the proteins found to be differentially expressed...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27607558/acute-ethanol-increases-igf-i-induced-phosphorylation-of-erks-by-enhancing-recruitment-of-p52-shc-to-the-grb2-shc-complex
#13
Matthew Dean, Adam Lassak, Anna Wilk, Adriana Zapata, Luis Marrero, Patricia Molina, Krzysztof Reiss
Ethanol plays a detrimental role in the development of the brain. Multiple studies have shown that ethanol inhibits insulin-like growth factor I receptor (IGF-IR) function. Because the IGF-IR contributes to brain development by supporting neural growth, survival, and differentiation, we sought to determine the molecular mechanism(s) involved in ethanol's effects on this membrane-associated tyrosine kinase. Using multiple neuronal cell types, we performed Western blot, immunoprecipitation, and GST-pulldowns following acute (1 - 24 hours) or chronic (3 weeks) treatment with ethanol...
September 8, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27594973/genome-wide-transcriptional-analysis-reveals-the-protection-against-hypoxia-induced-oxidative-injury-in-the-intestine-of-tibetans-via-the-inhibition-of-grb2-egfr-ptpn11-pathways
#14
Kang Li, Luobu Gesang, Zeng Dan, Lamu Gusang
The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27590859/down-regulation-of-brain-derived-neurotrophic-factor-and-its-signaling-components-in-the-brain-tissues-of-scrapie-experimental-animals
#15
Ting-Ting Wang, Chan Tian, Jing Sun, Hui Wang, Bao-Yun Zhang, Cao Chen, Jing Wang, Kang Xiao, Li-Na Chen, Yan Lv, Chen Gao, Qi Shi, Yan Xin, Xiao-Ping Dong
Prion is a unique nucleic acid-free pathogen that causes human and animal fatal neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. There are two distinct classes of glycosylated receptors, neurotrophin receptor p75 (p75NTR) and tropomyosin-related kinase (Trk), that can bind to BDNF. To obtain insights into the possible alterations of brain BDNF and its signaling pathway in prion disease, the levels of BDNF and several molecules in the BDNF pathway in the brain tissues of scrapie agents 263K-infected hamsters were separately evaluated...
October 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27587340/systemic-study-of-a-natural-feedback-loop-in-huntington-s-disease-at-the-onset-of-neurodegeneration
#16
Shounak Baksi, Sangram Bagh, Sandip Sarkar, Debashis Mukhopadhyay
Aggregation prone Huntingtin (Htt) protein and its aberrations, causing protein misfolding, have been the prototype of intense research for several decades. Misfolded aggregates or oligomers of different sizes not only deregulate the homeostasis, cellular machinery also counterbalances the effects at least at the initial stages, till the balance tilts towards toxicity and degeneration. In this paper, we combine experimental approaches with system based computational modeling to decipher the molecular mechanisms as well as the hidden dynamics leading to neuronal death in HD...
August 30, 2016: Bio Systems
https://www.readbyqxmd.com/read/27550373/the-dok-3-grb2-adaptor-module-promotes-inducible-association-of-the-lipid-phosphatase-ship-with-the-bcr-in-a-coreceptor-independent-manner
#17
Birgit Manno, Thomas Oellerich, Tim Schnyder, Jasmin Corso, Marion Lösing, Konstantin Neumann, Henning Urlaub, Facundo D Batista, Michael Engelke, Jürgen Wienands
The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. Here we demonstrate a coreceptor-independent membrane recruitment and function of SHIP in B cells...
August 23, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27543756/role-of-herpes-simplex-virus-1-vp11-12-tyrosine-based-binding-motifs-for-src-family-kinases-p85-grb2-and-shc-in-activation-of-the-phosphoinositide-3-kinase-akt-pathway
#18
Ulrike Strunk, Daniel Gomez Ramos, Holly A Saffran, James R Smiley
The abundant HSV-1 tegument protein VP11/12 encoded by gene UL46 is essential for induction of the PI3K/Akt-signaling pathway during infection. VP11/12 utilizes tyrosine-based motifs within its C-terminal region to bind the SH2 domains of Src family kinases, the p85 subunit of PI3 Kinase and Grb2, and the PTB domain of Shc. We previously proposed that the interaction with SFKs and p85 is used to gain control over the PI3K/Akt signaling pathway. We tested this model by evaluating the effects of mutations that eliminate each of these interactions on the ability of HSV-1 to activate Akt...
November 2016: Virology
https://www.readbyqxmd.com/read/27533249/aberrant-expression-of-mir-21-mir-376c-and-mir-145-and-their-target-host-genes-in-merkel-cell-polyomavirus-positive-non-small-cell-lung-cancer
#19
Ismini Lasithiotaki, Eliza Tsitoura, Anastasios Koutsopoulos, Eleni Lagoudaki, Chara Koutoulaki, George Pitsidianakis, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from "healthy" sites, distant from the tumour region that were either positive or negative for MCPyV DNA...
August 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27531744/homo-and-heterotypic-association-regulates-signaling-by-the-sgk269-peak1-and-sgk223-pseudokinases
#20
Ling Liu, Yu Wei Phua, Rachel S Lee, Xiuquan Ma, Yiping Jenkins, Karel Novy, Emily S Humphrey, Howard Chan, Robert Shearer, Poh Chee Ong, Weiwen Dai, Darren N Saunders, Isabelle S Lucet, Roger J Daly
SgK269/PEAK1 is a pseudokinase and scaffolding protein that plays a critical role in regulating growth factor receptor signal output and is implicated in the progression of several cancers, including those of the breast, colon, and pancreas. SgK269 is structurally related to SgK223, a human pseudokinase that also functions as a scaffold but recruits a distinct repertoire of signaling proteins compared with SgK269. Structural similarities between SgK269 and SgK223 include a predicted α-helical region (designated CH) immediately preceding the conserved C-terminal pseudokinase (PK) domain...
October 7, 2016: Journal of Biological Chemistry
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