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https://www.readbyqxmd.com/read/28720576/deubiquitinating-enzyme-usp9x-suppresses-tumor-growth-via-lats-kinase-and-core-components-of-the-hippo-pathway
#1
Aleksandra Toloczko, Fusheng Guo, Hiu-Fung Yuen, Qing Wen, Stephen Andrew Wood, Yan Shan Ong, Pei Yi Chan, Asfa Alli Shaik, Jayantha Gunaratne, Mark John Dunne, Wanjin Hong, Siew Wee Chan
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28718215/usp18-protects-against-hepatic-steatosis-and-insulin-resistance-via-its-dub-activity
#2
Shimin An, Ling-Ping Zhao, Li-Jun Shen, Siyuan Wang, Kuo Zhang, Yu Qi, Jilin Zheng, Xiao-Jing Zhang, Xue-Yong Zhu, Rong Bao, Ling Yang, Yue-Xin Lu, Zhi-Gang She, Yi-Da Tang
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, impaired insulin sensitivity and chronic low-grade inflammation. However, the pathogenic mechanism of NAFLD is poorly understood, which hinders the exploration of possible treatments. Here, we first report that ubiquitin-specific protease 18 (USP18), a member of the deubiquitinating (DUB) enzyme family, plays regulatory roles in NAFLD progression. The expression of USP18 was down-regulated in the livers of non-alcoholic steatohepatitis (NASH) patients and high-fat diet (HFD) induced or genetically obese mice...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28712728/hexim1-and-neat1-long-non-coding-rna-form-a-multi-subunit-complex-that-regulates-dna-mediated-innate-immune-response
#3
Mehdi Morchikh, Alexandra Cribier, Raoul Raffel, Sonia Amraoui, Julien Cau, Dany Severac, Emeric Dubois, Olivier Schwartz, Yamina Bennasser, Monsef Benkirane
The DNA-mediated innate immune response underpins anti-microbial defenses and certain autoimmune diseases. Here we used immunoprecipitation, mass spectrometry, and RNA sequencing to identify a ribonuclear complex built around HEXIM1 and the long non-coding RNA NEAT1 that we dubbed the HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex (HDP-RNP). The HDP-RNP contains DNA-PK subunits (DNAPKc, Ku70, and Ku80) and paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATRIN3). We show that binding of HEXIM1 to NEAT1 is required for its assembly...
July 10, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28710128/bcxyg1-a-secreted-xyloglucanase-from-botrytis-cinerea-induces-cell-death-and-triggers-plant-defense
#4
Wenjun Zhu, Mordechi Ronen, Yonatan Gur, Anna Minz-Dub, Gal Masrati, Nir Ben-Tal, Itai Sharon, Alon Savidor, Elad Eizner, Oliver Valerius, Gerhard Braus, Kyle Bowler, Maor Bar-Peled, Amir Sharon
In search of Botrytis cinerea cell death-inducing proteins, we found a xyloglucanase (BcXYG1), which induced strong necrosis and a resistance response in dicot plants. Expression of the BcXYG1 gene was strongly induced during the first 12 hours post inoculation, and analysis of disease dynamics using PathTrack{copyright, serif} showed that a B. cinerea strain over expressing BcXYG1 produced early local necrosis supporting a role of BcXYG1 as an early cell death-inducing factor. The xyloglucanase activity of BcXYG1 was not necessary for induction of necrosis and plant resistance, as a mutant of BcXYG1 lacking the xyloglucanase enzymatic activity retained both functions...
July 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28708543/proposal-flow-semantic-correspondences-from-object-proposals
#5
Bumsub Ham, Minsu Cho, Cordelia Schmid, Jean Ponce
Finding image correspondences remains a challenging problem in the presence of intra-class variations and large changes in scene layout. Semantic flow methods are designed to handle images depicting different instances of the same object or scene category. We introduce a novel approach to semantic flow, dubbed proposal flow, that establishes reliable correspondences using object proposals. Unlike prevailing semantic flow approaches that operate on pixels or regularly sampled local regions, proposal flow benefits from the characteristics of modern object proposals, that exhibit high repeatability at multiple scales, and can take advantage of both local and geometric consistency constraints among proposals...
July 11, 2017: IEEE Transactions on Pattern Analysis and Machine Intelligence
https://www.readbyqxmd.com/read/28701704/concatseq-a-method-for-increasing-throughput-of-single-molecule-sequencing-by-concatenating-short-dna-fragments
#6
Ulrich Schlecht, Janine Mok, Carolina Dallett, Jan Berka
Single molecule sequencing (SMS) platforms enable base sequences to be read directly from individual strands of DNA in real-time. Though capable of long read lengths, SMS platforms currently suffer from low throughput compared to competing short-read sequencing technologies. Here, we present a novel strategy for sequencing library preparation, dubbed ConcatSeq, which increases the throughput of SMS platforms by generating long concatenated templates from pools of short DNA molecules. We demonstrate adaptation of this technique to two target enrichment workflows, commonly used for oncology applications, and feasibility using PacBio single molecule real-time (SMRT) technology...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692038/par-terra-directs-homologous-sex-chromosome-pairing
#7
Hsueh-Ping Chu, John E Froberg, Barry Kesner, Hyun Jung Oh, Fei Ji, Ruslan Sadreyev, Stefan F Pinter, Jeannie T Lee
In mammals, homologous chromosomes rarely pair outside meiosis. One exception is the X chromosome, which transiently pairs during X-chromosome inactivation (XCI). How two chromosomes find each other in 3D space is not known. Here, we reveal a required interaction between the X-inactivation center (Xic) and the telomere in mouse embryonic stem (ES) cells. The subtelomeric, pseudoautosomal regions (PARs) of the two sex chromosomes (X and Y) also undergo pairing in both female and male cells. PARs transcribe a class of telomeric RNA, dubbed PAR-TERRA, which accounts for a vast majority of all TERRA transcripts...
July 10, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28682311/platinum-pyrithione-induces-apoptosis-in-chronic-myeloid-leukemia-cells-resistant-to-imatinib-via-dub-inhibition-dependent-caspase-activation-and-bcr-abl-downregulation
#8
Xiaoying Lan, Chong Zhao, Xin Chen, Peiquan Zhang, Dan Zang, Jinjie Wu, Jinghong Chen, Huidan Long, Li Yang, Hongbiao Huang, Xuejun Wang, Xianping Shi, Jinbao Liu
Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. T315I Bcr-Abl is the most notorious point mutation to elicit acquired resistance to imatinib (IM), leading to poor prognosis. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance. We recently reported that platinum pyrithione (PtPT) potently inhibits the ubiquitin-proteasome system (UPS) via targeting the 26 S proteasome-associated deubiquitinases (DUBs), without effecting on the 20 S proteasome...
July 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28682253/bilinear-optimized-product-quantization-for-scalable-visual-content-analysis
#9
Litao Yu, Zi Huang, Fumin Shen, Jingkuan Song, Heng Tao Shen, Xiaofang Zhou
Product quantization (PQ) has been recognized as a useful technique to encode visual feature vectors into compact codes to reduce both the storage and computation cost. Recent advances in retrieval and vision tasks indicate that high-dimensional descriptors are critical to ensuring high accuracy on large-scale datasets. However, optimizing PQ codes with high-dimensional data is extremely time and memory consuming. To solve this problem, in this paper, we present a novel PQ method based on bilinear projection, which can well exploit the natural data structure and reduce the computational complexity...
June 30, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/28679862/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#10
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28669195/anomalous-structural-disorder-in-supported-pt-nanoparticles
#11
Fernando D Vila, John J Rehr, Ralph G Nuzzo, Anatoly I Frenkel
Supported Pt nanocatalysts generally exhibit anomalous behavior, including negative thermal expansion and large structural disorder. Finite temperature DFT/MD simulations reproduce these properties, showing that they are largely explained by a combination of thermal vibrations and low-frequency disorder. We show here that a full interpretation is more complex and that the DFT/MD mean-square relative displacements (MSRD) can be further separated into vibrational disorder, "dynamic structural disorder" (DSD), and long-time equilibrium fluctuations of the structure dubbed "anomalous structural disorder" (ASD)...
July 6, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28660979/gel-seq-whole-genome-and-transcriptome-sequencing-by-simultaneous-low-input-dna-and-rna-library-preparation-using-semi-permeable-hydrogel-barriers
#12
Gordon D Hoople, Andrew Richards, Yan Wu, Kota Kaneko, Xiaolin Luo, Gen-Sheng Feng, Kun Zhang, Albert P Pisano
The advent of next generation sequencing has fundamentally changed genomics research. Unfortunately, standard protocols for sequencing the genome and the transcriptome are incompatible. This forces researchers to choose between examining either the DNA or the RNA for a particular sample. Here we describe a new device and method, collectively dubbed Gel-seq, that enables researchers to simultaneously sequence both DNA and RNA from the same sample. This technology makes it possible to directly examine the ways that changes in the genome impact the transcriptome in as few as 100 cells...
June 29, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28659380/deubiquitylation-of-deubiquitylases
#13
REVIEW
Saba Haq, Suresh Ramakrishna
Deubiquitylating enzymes (DUBs) reverse the ubiquitylation of target proteins, thereby regulating diverse cellular functions. In contrast to the plethora of research being conducted on the ability of DUBs to counter the degradation of cellular proteins or auto-ubiquitylated E3 ligases, very little is known about the mechanisms of DUB regulation. In this review paper, we summarize a novel possible mechanism of DUB deubiquitylation by other DUBs. The available data suggest the need for further experiments to validate and characterize this notion of 'Dubbing DUBs'...
June 2017: Open Biology
https://www.readbyqxmd.com/read/28655766/a-new-approach-for-generating-bispecific-antibodies-based-on-a-common-light-chain-format-and-the-stable-architecture-of-human-immunoglobulin-g1
#14
Camilla De Nardis, Linda J A Hendriks, Emilie Poirier, Tudor Arvinte, Piet Gros, Alexander B H Bakker, John de Kruif
Bispecific antibodies combine two different antigen binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability and pharmacokinetic properties. Here we describe a new approach for generating bispecific antibodies using a common light chain format and exploiting the stable architecture of human immunoglobulin G1...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637836/bacterial-cellulose-shifts-transcriptome-and-proteome-of-cultured-endothelial-cells-towards-native-differentiation
#15
Gerhard Feil, Ralf Horres, Julia Schulte, Andreas F Mack, Svenja Petzoldt, Caroline Arnold, Chen Meng, Lukas Jost, Jochen Boxleitner, Nicole Kiessling-Wolf, Ender Serbest, Dominic Helm, Bernhard Kuster, Isabel Hartmann, Thomas Korff, Hannes Hahne
Preserving the native phenotype of primary cells in vitro is a complex challenge. Recently, hydrogel-based cellular matrices have evolved as alternatives to conventional cell culture techniques. We developed a bacterial cellulose-based aqueous gel-like biomaterial, dubbed Xellulin, which mimics a cellular microenvironment and seems to maintain the native phenotype of cultured and primary cells. When applied to human umbilical vein endothelial cells (HUVEC), it allowed the continuous cultivation of cell monolayers for more than one year without degradation or dedifferentiation...
June 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28618495/robustness-of-synthetic-oscillators-in-growing-and-dividing-cells
#16
Joris Paijmans, David K Lubensky, Pieter Rein Ten Wolde
Synthetic biology sets out to implement new functions in cells, and to develop a deeper understanding of biological design principles. Elowitz and Leibler [Nature (London) 403, 335 (2000)NATUAS0028-083610.1038/35002125] showed that by rational design of the reaction network, and using existing biological components, they could create a network that exhibits periodic gene expression, dubbed the repressilator. More recently, Stricker et al. [Nature (London) 456, 516 (2008)NATUAS0028-083610.1038/nature07389] presented another synthetic oscillator, called the dual-feedback oscillator, which is more stable...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28617443/bilirubin-neurotoxicity-is-associated-with-proteasome-inhibition
#17
Hongbiao Huang, Mingxing Guo, Ningning Liu, Chong Zhao, Haoyu Chen, Xiaoli Wang, Siyan Liao, Ping Zhou, Yuning Liao, Xin Chen, Xiaoying Lan, Jinghong Chen, Dacai Xu, Xiaofen Li, Xianping Shi, Li Yu, Yuqiang Nie, Xuejun Wang, Chang-E Zhang, Jinbao Liu
The molecular mechanism underlying bilirubin neurotoxicity remains obscure. Ubiquitin-proteasome system-mediated proteolysis is pivotal to virtually all cellular processes and cell survival. Here we report for the first time that bilirubin at a clinically relevant elevated level impairs proteasomal function via inhibiting both the 19S proteasome-associated deubiquitinases (USP14 and UCHL5) and the chymotrypsin-like (CT-like) peptidase activity of 20S proteasomes, thereby contributing to bilirubin neurotoxicity...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28606465/ubiquitin-proteasome-system-and-er-stress-in-the-retina-of-diabetic-rats
#18
Karnam Shruthi, Singareddy Sreenivasa Reddy, Geereddy Bhanuprakash Reddy
PURPOSE: Diabetic retinopathy (DR) is the most frequently occurring complication of diabetes. Alterations in ubiquitin-proteasome system (UPS) have been associated with several degenerative disorders. Hence, in this study, we investigated the status and role of UPS and ER stress in the retina of diabetic rats. METHODS: Diabetes was induced in rats by streptozotocin. Retinal markers, ER stress markers, components of UPS, ERAD, and autophagy were analyzed after 2- and 4-months of diabetes...
August 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28604766/the-deubiquitinating-enzymes-usp4-and-usp17-target-hyaluronan-synthase-2-and-differentially-affect-its-function
#19
M Mehić, V K de Sa, S Hebestreit, C-H Heldin, P Heldin
The levels of hyaluronan, a ubiquitous glycosaminoglycan prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20). Hyaluronan accumulates in rapidly remodeling tissues, such as breast cancer, due to deregulated expression of the HAS2 gene and/or alterations of HAS2 activity. The activity of HAS2 is regulated by post-translational modifications, including ubiquitination. In order to identify deubiquitinating enzymes (DUBs) that are involved in de-ubiquitination of HAS2, a complementary (cDNA) library of 69 Flag-HA-tagged human DUBs cloned into retroviral vectors was screened in human embryonic kidney (HEK) 293T cells for their ability to de-ubiquitinate myc-tagged HAS2...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604753/let-7b-and-let-7c-micrornas-promote-histone-h2b-ubiquitylation-and-inhibit-cell-migration-by-targeting-multiple-components-of-the-h2b-deubiquitylation-machinery
#20
A Spolverini, G Fuchs, D R Bublik, M Oren
Monoubiquitylation of histone H2B (H2Bub1) is catalyzed mainly by the RNF20/RNF40 complex and erased by multiple deubiquitylating enzymes (DUBs). H2Bub1 influences many aspects of chromatin function, including transcription regulation and DNA repair. Cancer cells often display reduced levels of H2Bub1, and this reduction may contribute to cancer progression. The let-7 family of microRNAs (miRNAs) comprises multiple members with reported tumor-suppressive features, whose expression is frequently downregulated in cancer...
June 12, 2017: Oncogene
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