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https://www.readbyqxmd.com/read/28106985/transparent-window-vibrational-probes-for-the-characterization-of-proteins-with-high-structural-and-temporal-resolution
#1
Ramkrishna Adhikary, Jörg Zimmermann, Floyd E Romesberg
Vibrational spectroscopy provides a direct route to the physicochemical characterization of molecules. While both IR and Raman spectroscopy have been used for decades to provide detailed characterizations of small molecules, similar studies with proteins are largely precluded due to spectral congestion. However, the vibrational spectra of proteins do include a "transparent window", between ∼1800 and ∼2500 cm(-1), and progress is now being made to develop site-specifically incorporated carbon-deuterium (C-D), cyano (CN), thiocyanate (SCN), and azide (N3) "transparent window vibrational probes" that absorb within this window and report on their environment to facilitate the characterization of proteins with small molecule-like detail...
January 20, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28105185/lim-and-sh3-protein-1-promotes-tumor-proliferation-and-metastasis-in-lung-carcinoma
#2
Xueqiong Lin, Xianhui Liu, Yusen Fang, Xuefen Weng
Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. In the present study, we focused on LIM and SH3 protein 1 (LASP-1), a key molecule involved in the development of multiple cancers, and attempted to elucidate its effect on the oncogenesis of lung cancer. We determined the expression level of LASP-1 in lung cancer using reverse transcription-quantitative polymerase chain reaction and western blot analysis, and also studied the potential function of LASP-1 in lung cancer cell growth, apoptosis and migration by small interfering RNA transfection...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105178/prognostic-relevance-of-samsn1-expression-in-gastric-cancer
#3
Mitsuro Kanda, Dai Shimizu, Satoshi Sueoka, Shuji Nomoto, Hisaharu Oya, Hideki Takami, Kazuhiro Ezaka, Ryoji Hashimoto, Yuri Tanaka, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
The prognosis for patients with advanced gastric cancer (GC) remains poor. The identification of biomarkers relevant to the recurrence and metastasis of GC is advantageous for stratifying patients and proposing novel molecular targets. In the present study the oncological roles of SAM domain, SH3 domain and nuclear localization signals 1 (SAMSN1), a mediator of B-cell function, were elucidated in GC. The expression and methylation status of SAMSN1 were investigated in a panel of 11 GC cell lines. Immunohistochemical staining was performed to determine the pattern of SAMSN1 protein expression in gastric tissues...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104453/alphavirus-polymerase-and-rna-replication
#4
REVIEW
Maija K Pietilä, Kirsi Hellström, Tero Ahola
Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands...
January 16, 2017: Virus Research
https://www.readbyqxmd.com/read/28104445/the-sh3-domain-of-caskin1-binds-to-lysophosphatidic-acid-suggesting-a-direct-role-for-the-lipid-in-intracellular-signaling
#5
Kitti Koprivanacz, Orsolya Tőke, Balázs Besztercei, Tünde Juhász, László Radnai, Balázs Merő, Judith Mihály, Mária Péter, Gábor Balogh, László Vígh, László Buday, Károly Liliom
Src homology 3 or SH3 domains constitute one of the most common protein domains in signal transduction, generally characterized by their binding to proline-rich sequences on interacting signaling proteins. Caskin1, a scaffold protein regulating cortical actin filaments, enriched in neural synapses in mammals, has an atypical SH3 domain. Key aromatic residues necessary for ligand binding that are present in canonical SH3 domains are missing from Caskin1 SH3. In concordance, proline-rich interacting partner could not be identified yet...
January 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28101242/screening-and-analysis-of-breast-cancer-genes-regulated-by-the-human-mammary-microenvironment-in-a-humanized-mouse-model
#6
Mingjie Zheng, Jue Wang, Lijun Ling, Dandan Xue, Shui Wang, Yi Zhao
Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28096337/stress-granule-associated-protein-g3bp2-regulates-breast-tumor-initiation
#7
Nisha Gupta, Mark Badeaux, Yiqian Liu, Kamila Naxerova, Dennis Sgroi, Lance L Munn, Rakesh K Jain, Igor Garkavtsev
Breast tumors contain tumorigenic cancer cells, termed "tumor-initiating cells" (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small molecules that enhance the effect of chemotherapeutic agents on TIC-enriched breast cancer cells. We identified proteins that interact with the lead compound C108, including the stress granule-associated protein, GTPase-activating protein (SH3 domain)-binding protein 2, G3BP2...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28078722/ssb-and-the-recg-dna-helicase-an-intimate-association-to-rescue-a-stalled-replication-fork
#8
REVIEW
Piero R Bianco, Yuri L Lyubchenko
In E. coli, the regression of stalled DNA replication forks is catalyzed by the DNA helicase RecG. One means of gaining access to the fork is by binding to the single strand binding protein or SSB. This interaction occurs via the wedge domain of RecG and the intrinsically disordered linker (IDL) of SSB, in a manner similar to that of SH3 domains binding to PXXP motif-containing ligands in eukaryotic cells. During loading, SSB remodels the wedge domain so that the helicase domains bind to the parental, duplex DNA, permitting the helicase to translocate using thermal energy...
January 12, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28067252/two-step-amyloid-aggregation-sequential-lag-phase-intermediates
#9
Fabio Castello, Jose M Paredes, Maria J Ruedas-Rama, Miguel Martin, Mar Roldan, Salvador Casares, Angel Orte
The self-assembly of proteins into fibrillar structures called amyloid fibrils underlies the onset and symptoms of neurodegenerative diseases, such as Alzheimer's and Parkinson's. However, the molecular basis and mechanism of amyloid aggregation are not completely understood. For many amyloidogenic proteins, certain oligomeric intermediates that form in the early aggregation phase appear to be the principal cause of cellular toxicity. Recent computational studies have suggested the importance of nonspecific interactions for the initiation of the oligomerization process prior to the structural conversion steps and template seeding, particularly at low protein concentrations...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28060514/targeted-covalent-inhibition-of-grb2-sos1-interaction-through-proximity-induced-conjugation-in-breast-cancer-cells
#10
Yongsheng Yu, Yunyu Nie, Qian Feng, Jiale Qu, Rui Wang, Liming Bian, Jiang Xia
Targeted covalent inhibitors of protein-protein interactions differ from reversible inhibitors in that the former bind and covalently bond the target protein at a specific site of the target. The site specificity is the result of the proximity of two reactive groups at the bound state, for example one mild electrophile in the inhibitor and a natural cysteine in the target close to the ligand binding site. Only a few pharmaceutically relevant proteins have this structural feature. Grb2, a key adaptor protein in maintaining the ERK activity via binding Sos1 to activated RTKs, is one: the N-terminal SH3 domain of Grb2 (Grb2N-SH3) carries a unique solvent-accessible cysteine Cys32 close to its Sos1-binding site...
January 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28057797/prmt2-interacts-with-splicing-factors-and-regulates-the-alternative-splicing-of-bcl-x
#11
Mynol I Vhuiyan, Magnolia L Pak, Margaret A Park, Dylan Thomas, Ted M Lakowski, Charles E Chalfant, Adam Frankel
Protein arginine N-methyltransferase 2 (PRMT2) functions in JAK-STAT and Wnt/β-catenin signaling pathways, serves as a nuclear receptor-dependent transcriptional co-activator, and represses NF-κB and E2F1 transcription factor activities to promote apoptosis. We have previously demonstrated that PRMT2 interacts with PRMT1 and increases its activity. Here, we reveal associations using proteomics between the PRMT2 SH3 domain and splicing factors including Src-associated in mitosis 68 kDa protein (SAM68), a PRMT1 substrate and trans-acting factor that mediates BCL-X alternative splicing...
January 5, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28053107/domain-organization-and-evolution-of-the-highly-divergent-5-coding-region-of-genomes-of-arteriviruses-including-the-novel-possum-nidovirus
#12
Anastasia Gulyaeva, Magdalena Dunowska, Erik Hoogendoorn, Julia Giles, Dmitry Samborskiy, Alexander E Gorbalenya
: In five experimentally characterized arterivirus species, the 5' -end genome coding region comprises most divergent nonstructural proteins (nsp) 1 and 2 that include papain-like proteases (PLPs) and other poorly characterized domains. They are involved in regulation of transcription, polyprotein processing, and virus-host interaction. Here, we present results of bioinformatics analysis of this region of 14 arterivirus species, including that of the most distantly related wobbly possum disease virus (WPDV), determined by a modified 5' RACE protocol...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28018665/domain-specific-functions-of-stardust-in-drosophila-embryonic-development
#13
Leonie Koch, Sabine Feicht, Rui Sun, Arnab Sen, Michael P Krahn
In Drosophila, the adaptor protein Stardust is essential for the stabilization of the polarity determinant Crumbs in various epithelial tissues, including the embryonic epidermis, the follicular epithelium and photoreceptor cells of the compound eye. In turn, Stardust recruits another adaptor protein, PATJ, to the subapical region to support adherens junction formation and morphogenetic events. Moreover, Stardust binds to Lin-7, which is dispensable in epithelial cells but functions in postsynaptic vesicle fusion...
November 2016: Royal Society Open Science
https://www.readbyqxmd.com/read/28017636/identification-and-first-characterization-of-smeps8-a-potential-interaction-partner-of-smtk3-and-ser-transcribed-in-the-gonads-of-schistosoma-mansoni
#14
C Buro, C Burmeister, T Quack, C G Grevelding
In eukaryotes the roles of protein kinases (PKs) regulating important biological processes such as growth and differentiation are well known. Molecular, biochemical, and physiological analyses trying to unravel principles of schistosome development have substantiated the importance for PKs also in this parasite. Amongst others the role of SmTK3 was studied, one of the first cellular PKs characterized from Schistosoma mansoni. Its function was demonstrated in mitogenic and differentiation processes in the gonads...
December 22, 2016: Experimental Parasitology
https://www.readbyqxmd.com/read/28011284/phosphorylation-of-tudor-sn-a-novel-substrate-of-jnk-is-involved-in-the-efficient-recruitment-of-tudor-sn-into-stress-granules
#15
Chao Su, Xingjie Gao, Wendong Yang, Yali Zhao, Xue Fu, Xiaoteng Cui, Chunyan Zhang, Lingbiao Xin, Yuanyuan Ren, Lixin Li, Wenqing Shui, Xi Yang, Minxin Wei, Jie Yang
Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite...
December 21, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28008818/deletion-of-a-putative-nlpc-p60-endopeptidase-bas1812-affects-germination-long-term-survival-and-endospore-formation-in-bacillus-anthracis
#16
Se Kye Kim, Yun Min Park, Kyoung Hwa Jung, Young Gyu Chai
Bacillus anthracis, an etiologic agent of the zoonotic disease anthrax, encodes a putative NlpC/P60 endopeptidase BAS1812. It harbors a signal peptide, three bacterial SH3 domains and an NlpC/P60 family domain. Previous studies showed that BAS1812 is immunogenic in infected hosts and is a potential biomarker for anthrax treatment. To date, however, little information is known about its function and involvement in anthrax pathogenesis. Here we describe the phenotypic effect of BAS1812 deletion in B. anthracis Sterne strain...
December 23, 2016: Microbiology
https://www.readbyqxmd.com/read/28003463/congenital-myopathy-results-from-misregulation-of-a-muscle-ca2-channel-by-mutant-stac3
#17
Jeremy W Linsley, I-Uen Hsu, Linda Groom, Viktor Yarotskyy, Manuela Lavorato, Eric J Horstick, Drew Linsley, Wenjia Wang, Clara Franzini-Armstrong, Robert T Dirksen, John Y Kuwada
Skeletal muscle contractions are initiated by an increase in Ca(2+) released during excitation-contraction (EC) coupling, and defects in EC coupling are associated with human myopathies. EC coupling requires communication between voltage-sensing dihydropyridine receptors (DHPRs) in transverse tubule membrane and Ca(2+) release channel ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum (SR). Stac3 protein (SH3 and cysteine-rich domain 3) is an essential component of the EC coupling apparatus and a mutation in human STAC3 causes the debilitating Native American myopathy (NAM), but the nature of how Stac3 acts on the DHPR and/or RyR1 is unknown...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28002633/vta-da-neuron-excitatory-synapses-in-shank3-%C3%AE-ex-4-9-mouse-line
#18
Bariselli Sebastiano, Bellone Camilla
SHANK3 proteins belong to the Shank/ProSAP family, which contain five-conserved domains - the ankyrin (ANK) repeated, the Src homology 3 (SH3), the PSD-95/Discs large/ZO-1 (PDZ), the proline-rich and the sterile alpha motif (SAM; Sheng and Kim, 2000). SHANK proteins are located at the postsynaptic density of excitatory synapses and indirectly link the metabotropic (mGluRs) and the ionotropic glutamate receptor (iGluRs: AMPARs, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and NMDARs, N-methyl-D-aspartate receptors) via different domains (Naisbitt et al...
December 21, 2016: Synapse
https://www.readbyqxmd.com/read/27965114/myogenic-differentiation-depends-on-the-interplay-of-grb2-and-n-wasp
#19
Payal Mitra, Thirumaran Thanabalu
Myogenesis requires a well-coordinated withdrawal from cell cycle, morphological changes and cell fusion mediated by actin cytoskeleton. Grb2 is an adaptor protein whose central SH2 domain binds to phosphorylated tyrosine residues of activated receptors and activates intracellular signaling pathway, while its N-terminal and C-terminal SH3 domains bind to proline rich proteins such as N-WASP (Neural-Wiskott Aldrich Syndrome Protein). We found that the expression of Grb2 was increased at the beginning of differentiation and remained constant during differentiation in C2C12 myoblasts...
December 10, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27938497/silencing-of-lim-and-sh3-protein-1-lasp-1-inhibits-thyroid-cancer-cell-proliferation-and-invasion
#20
Wei Gao, Jiakai Han
LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein that was firstly identified from breast cancer andthen reported to be involved in cell proliferation and migration. Many studies have demonstrated the essential role of LASP-1 in cancer progression. But there have been no studies on the association of LASP-1 with thyroid cancer. In this study, we investigated the expression pattern and biological function of LASP-1 in thyroid cancer. We found that LASP-1 was highly expressed in thyroid cancer tissues and cell lines...
November 17, 2016: Oncology Research
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