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https://www.readbyqxmd.com/read/28534512/a-viral-microrna-downregulates-metastasis-suppressor-cd82-and-induces-cell-invasion-and-angiogenesis-by-activating-the-c-met-signaling
#1
W Li, M Hu, C Wang, H Lu, F Chen, J Xu, Y Shang, F Wang, J Qin, Q Yan, B J Krueger, R Renne, S-J Gao, C Lu
Kaposi's sarcoma (KS) as the most common AIDS-associated malignancy is etiologically caused by KS-associated herpesvirus (KSHV). KS is a highly disseminated and vascularized tumor. KSHV encodes 12 pre-microRNAs that yield 25 mature microRNAs (miRNAs), but their roles in KSHV-induced tumor metastasis and angiogenesis remain largely unclear. KSHV-encoded miR-K12-6 (miR-K6) can generate two mature miRNAs, miR-K6-5p and miR-K6-3p. Recently, we have shown that miR-K6-3p induced cell migration and angiogenesis via directly targeting SH3 domain binding glutamate-rich protein (SH3BGR)...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#2
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28530710/engineering-protein-stability-with-atomic-precision-in-a-monomeric-miniprotein
#3
Emily G Baker, Christopher Williams, Kieran L Hudson, Gail J Bartlett, Jack W Heal, Kathryn L Porter Goff, Richard B Sessions, Matthew P Crump, Derek N Woolfson
Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 °C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPα is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28523344/role-of-g3bp1-in-glucocorticoid-receptor-mediated-microrna-15b-and-microrna-23a-biogenesis-in-endothelial-cells
#4
Hoi-Hin Kwok, Po-Ying Poon, Kylie Hin-Man Mak, Lin-Yao Zhang, Pei Liu, Huoming Zhang, Nai-Ki Mak, Patrick Ying-Kit Yue, Ricky Ngok-Shun Wong
MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells...
May 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28522963/the-f-actin-binding-protein-cortactin-regulates-the-dynamics-of-the-exocytotic-fusion-pore-through-its-sh3-domain
#5
Arlek M González-Jamett, María J Guerra, María J Olivares, Valentina Haro-Acuña, Ximena Baéz-Matus, Jacqueline Vásquez-Navarrete, Fanny Momboisse, Narcisa Martinez-Quiles, Ana M Cárdenas
Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca(2+) signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28510117/novex-3-the-tiny-titin-of-muscle
#6
REVIEW
Dalma Kellermayer, John E Smith, Henk Granzier
The giant multi-functional striated muscle protein titin is the third most abundant muscle protein after myosin and actin. Titin plays a pivotal role in myocardial passive stiffness, structural integrity and stress-initiated signaling pathways. The complete sequence of the human titin gene contains three isoform-specific mutually exclusive exons [termed novel exons (novex)] coding for the I-band sequence, named novex-1 (exon 45), novex-2 (exon 46) and novex-3 (exon 48). Transcripts containing either the novex-1 or novex-2 exons code for the novex-1 and novex-2 titin isoforms...
April 7, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28502111/asap3-upregulation-contributes-to-colorectal-carcinogenesis-and-indicates-poor-survival-outcome
#7
Haiying Tian, Jin Qian, Luoyan Ai, Yueyuan Li, Wenyu Su, Xian-Ming Kong, Jie Xu, Jing-Yuan Fang
The function and clinical implication of ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the present study, we showed that the expression level of ASAP3 was dramatically increased in CRC and its upregulation was associated with American Joint Committee on Cancer (AJCC) stage (P<0.001) and poor prognosis (P=0.0022). The combination of AJCC stage and ASAP3 expression improved the prediction of survival in CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G1-phase arrest without influencing apoptosis...
May 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28479222/effects-of-a-spleen-tyrosine-kinase-inhibitor-on-progression-of-the-lupus-nephritis-in-mice
#8
Maki Kitai, Noboru Fukuda, Takahiro Ueno, Morito Endo, Takashi Maruyama, Masanori Abe, Kazuyoshi Okada, Masayoshi Soma, Koichi Matsumoto
The Fc receptors (FcR) have pivotal roles in the pathogenesis of the autoimmune glomerulonephritis. We therefore investigated the effects of a Syk inhibitor on the progression of lupus nephritis and SH3 domain binding protein 2 and p38MAP kinase signalings in mice. NZB/W F1 mice, a model of lupus nephritis, received a Syk inhibitor R406. Western blotting and immunohistochemistry revealed that R406 treatment significantly delayed the appearance of proteinuria, histologically improved their glomerulosclerosis and inhibited the increased the expression of MCP-1 and TGF-β1 mRNAs and the nephrin and podocin proteins in the kidney...
March 25, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28477416/systematic-identification-and-competitive-disruption-of-securin-binding-partners-in-the-gene-diversity-space-of-human-colorectal-cancer
#9
Yinguang Zhang, Yongwang Zhang, Yuxiang Zhang
Human securin is regulatory protein involved in control of the metaphase-anaphase transition and anaphase onset of colorectal cancer. Molecular evidences suggest that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich peptides. In this study, we have performed a genome-wide analysis and identification of securin-binding partners in the gene diversity space of human colorectal cancer. The securin-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular assay...
May 6, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28470949/loss-of-sh3gl2-promotes-the-migration-and-invasion-behaviours-of-glioblastoma-cells-through-activating-the-stat3-mmp2-signalling
#10
Yufu Zhu, Xiang Zhang, Lei Wang, Zhe Ji, Manyi Xie, Xinyu Zhou, Zhiyi Liu, Hengliang Shi, Rutong Yu
SH3GL2 (Src homology 3 (SH3) domain GRB2-like 2) is mainly expressed in the central nervous system and regarded as a tumour suppressor in human glioma. However, the molecular mechanism of the SH3GL2 protein involved in malignant behaviours of human glioma has not been elucidated. In this study, we tried to investigate the role of SH3GL2 in glioma cell migration and invasion and explore its underlined molecular mechanism. Firstly, we discovered that the protein level of SH3GL2 was widely decreased in the human glioma patients, especially in high-grade glioma tissues...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28465529/wnt5a-induces-ror1-to-complex-with-hs1-to-enhance-migration-of-chronic-lymphocytic-leukemia-cells
#11
K Hasan, J Yu, L Chen, B Cui, G F Widhopf, L Rassenti, Z Shen, S P Briggs, T J Kipps
ROR1 is a conserved, oncoembryonic surface-antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with Hematopoietic-lineage-cell-Specific protein 1 (HS1) in freshly-isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA, and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extra-cellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation...
May 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28456200/microscopic-insight-into-thermodynamics-of-conformational-changes-of-sap-slam-complex-in-signal-transduction-cascade
#12
Sudipta Samanta, Sanchita Mukherjee
The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex...
April 28, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28455498/grb2-carboxyl-terminal-sh3-domain-can-bivalently-associate-with-two-ligands-in-an-sh3-dependent-manner
#13
Richa Arya, Rohit Singh Dangi, Pinakin K Makwana, Ambrish Kumar, Santosh Kumar Upadhyay, Monica Sundd
Src homology domain containing leukocyte protein of 65 kDa (SLP65), the growth factor receptor binding protein 2 (Grb2), and the guanine nucleotide exchange factor for the Rho family GTPases (Vav), self associate in unstimulated B cells as components of the preformed B cell receptor transducer module, in an SH3-dependent manner. The complex enables the B cell to promptly respond to BCR aggregation, resulting in signal amplification. It also facilitates Vav translocation to the membrane rafts, for activation...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28437077/peptide-and-protein-dynamics-and-low-temperature-dnp-magic-angle-spinning-nmr
#14
Qing Zhe Ni, Evgeny Markhasin, Thach V Can, Björn Corzilius, Kong Ooi Tan, Alexander B Barnes, Eugenio Daviso, Yongchao Su, Judith Herzfeld, Robert G Griffin
In DNP MAS NMR experiments at ∼80-110 K, the structurally important -(13)CH3 and -(15)NH3(+) signals in MAS spectra of biological samples disappear due to the interference of the molecular motions with the (1)H decoupling. Here we investigate the effect of these dynamic processes on the NMR line shapes and signal intensities in several typical systems: (1) microcrystalline APG, (2) membrane protein bR, (3) amyloid fibrils PI3-SH3, (4) monomeric alanine-CD3, and (5) the protonated and deuterated dipeptide N-Ac-VL over 78-300 K...
May 10, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28429417/immobilization-methods-for-the-rapid-total-chemical-synthesis-of-proteins-on-microtiter-plates
#15
Robert Zitterbart, Michael Krumrey, Oliver Seitz
The chemical synthesis of proteins typically involves the solid-phase peptide synthesis of unprotected peptide fragments that are stitched together in solution by native chemical ligation (NCL). The process is slow, and throughput is limited because of the need for repeated high performance liquid chromatography purification steps after both solid-phase peptide synthesis and NCL. With an aim to provide faster access to functional proteins and to accelerate the functional analysis of synthetic proteins by parallelization, we developed a method for the high performance liquid chromatography-free synthesis of proteins on the surface of microtiter plates...
April 21, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28429360/effects-of-silencing-annexin-a5-on-proliferation-and-invasion-of-human-cholangiocarcinoma-cell-line
#16
X-M Ding, J-X Li, K Wang, Z-S Wu, A-H Yao, C-Y Jiao, J-J Qian, D-S Bai, X-C Li
OBJECTIVE: We investigated the expression of annexin A5 (ANXA5) in human cholangiocarcinoma (CCA) cell line and its effect on proliferation, migration, and apoptosis of human CCA cells. MATERIALS AND METHODS: Expression of ANXA5 was detected by fluorescent quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting method in 2 human CCA cell lines, QBC939 and RBE. 3 shRNA plasmids for ANXA5 silencing (ANXA5-sh1, ANXA5-sh2, ANXA5-sh3) and 1 negative control plasmid were constructed to infect QBC939 cells...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28426660/exhaustive-search-of-linear-information-encoding-protein-peptide-recognition
#17
Abdellali Kelil, Benjamin Dubreuil, Emmanuel D Levy, Stephen W Michnick
High-throughput in vitro methods have been extensively applied to identify linear information that encodes peptide recognition. However, these methods are limited in number of peptides, sequence variation, and length of peptides that can be explored, and often produce solutions that are not found in the cell. Despite the large number of methods developed to attempt addressing these issues, the exhaustive search of linear information encoding protein-peptide recognition has been so far physically unfeasible...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28426203/tyrosine-kinase-activation-and-conformational-flexibility-lessons-from-src-family-tyrosine-kinases
#18
Yilin Meng, Matthew P Pond, Benoît Roux
Protein kinases are enzymes that catalyze the covalent transfer of the γ-phosphate of an adenosine triphosphate (ATP) molecule onto a tyrosine, serine, threonine, or histidine residue in the substrate and thus send a chemical signal to networks of downstream proteins. They are important cellular signaling enzymes that regulate cell growth, proliferation, metabolism, differentiation, and migration. Unregulated protein kinase activity is often associated with a wide range of diseases, therefore making protein kinases major therapeutic targets...
April 20, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28414301/striatopallidal-dysfunction-underlies-repetitive-behavior-in-shank3-deficient-model-of-autism
#19
Wenting Wang, Chenchen Li, Qian Chen, Marie-Sophie van der Goes, James Hawrot, Annie Y Yao, Xian Gao, Congyi Lu, Ying Zang, Qiangge Zhang, Katherine Lyman, Dongqing Wang, Baolin Guo, Shengxi Wu, Charles R Gerfen, Zhanyan Fu, Guoping Feng
The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414299/an-indirect-route-to-repetitive-actions
#20
David M Lovinger
It is increasingly evident that there is a genetic contribution to autism spectrum disorders (ASDs) and other neural disorders involving excessive repetition of action sequences. Among the implicated genes in these disorders are those encoding postsynaptic scaffolding proteins with roles in synaptic transmission and plasticity. Several mouse models harboring synonymous mutations have shown alterations in synaptic transmission within the striatum, which has key roles in controlling actions and action sequences...
May 1, 2017: Journal of Clinical Investigation
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