keyword
MENU ▼
Read by QxMD icon Read
search

Anti crispr

keyword
https://www.readbyqxmd.com/read/28437394/selective-degradation-of-splicing-factor-caper%C3%AE-by-anticancer-sulfonamides
#1
Taisuke Uehara, Yukinori Minoshima, Koji Sagane, Naoko Hata Sugi, Kaoru Ogawa Mitsuhashi, Noboru Yamamoto, Hiroshi Kamiyama, Kentaro Takahashi, Yoshihiko Kotake, Mai Uesugi, Akira Yokoi, Atsushi Inoue, Taku Yoshida, Miyuki Mabuchi, Akito Tanaka, Takashi Owa
Target-protein degradation is an emerging field in drug discovery and development. In particular, the substrate-receptor proteins of the cullin-ubiquitin ligase system play a key role in selective protein degradation, which is an essential component of the anti-myeloma activity of immunomodulatory drugs (IMiDs), such as lenalidomide. Here, we demonstrate that a series of anticancer sulfonamides NSC 719239 (E7820), indisulam, and NSC 339004 (chloroquinoxaline sulfonamide, CQS) induce proteasomal degradation of the U2AF-related splicing factor coactivator of activating protein-1 and estrogen receptors (CAPERα) via CRL4(DCAF15) mediated ubiquitination in human cancer cell lines...
April 24, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28436707/samhd1-protects-cancer-cells-from-various-nucleoside-based-antimetabolites
#2
Nikolas Herold, Sean G Rudd, Kumar Sanjiv, Juliane Kutzner, Julia Bladh, Cynthia B J Paulin, Thomas Helleday, J I Henter, Torsten Schaller
Recently, we demonstrated that sterile alpha motif and HD domain containing protein 1 (SAMHD1) is a major barrier in acute myelogenous leukemic (AML) cells to the cytotoxicity of cytarabine (ara-C), the most important drug in AML treatment. Ara-C is intracellularly converted by the canonical dNTP synthesis pathway to ara-CTP, which serves as a substrate but not an allosteric activator of SAMHD1. Using an AML mouse model, we show here that wild type but not catalytically inactive SAMHD1 reduces ara-C treatment efficacy in vivo...
April 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28430577/synthetic-lethal-interaction-between-the-tumour-suppressor-stag2-and-its-paralog-stag1
#3
Lorena Benedetti, Matteo Cereda, LeeAnn Monteverde, Nikita Desai, Francesca D Ciccarelli
Cohesin is a multi-protein complex that tethers sister chromatids during mitosis and mediates DNA repair, genome compartmentalisation and regulation of gene expression. Cohesin subunits frequently acquire cancer loss-of-function alterations and act as tumour suppressors in several tumour types. This has led to increased interest in cohesin as potential target in anti-cancer therapy. Here we show that the loss-of-function of STAG2, a core component of cohesin and an emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells on its paralog STAG1...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423309/the-natural-product-cavinafungin-selectively-interferes-with-zika-and-dengue-virus-replication-by-inhibition-of-the-host-signal-peptidase
#4
David Estoppey, Chia Min Lee, Marco Janoschke, Boon Heng Lee, Kah Fei Wan, Hongping Dong, Philippe Mathys, Ireos Filipuzzi, Tim Schuhmann, Ralph Riedl, Thomas Aust, Olaf Galuba, Gregory McAllister, Carsten Russ, Martin Spiess, Tewis Bouwmeester, Ghislain M C Bonamy, Dominic Hoepfner
Flavivirus infections by Zika and dengue virus impose a significant global healthcare threat with no US Food and Drug Administration (FDA)-approved vaccination or specific antiviral treatment available. Here, we present the discovery of an anti-flaviviral natural product named cavinafungin. Cavinafungin is a potent and selectively active compound against Zika and all four dengue virus serotypes. Unbiased, genome-wide genomic profiling in human cells using a novel CRISPR/Cas9 protocol identified the endoplasmic-reticulum-localized signal peptidase as the efficacy target of cavinafungin...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28415820/targeting-programmed-cell-death-ligand-1-by-crispr-cas9-in-osteosarcoma-cells
#5
Yunfei Liao, Lulu Chen, Yong Feng, Jacson Shen, Yan Gao, Gregory Cote, Edwin Choy, David Harmon, Henry Mankin, Francis Hornicek, Zhenfeng Duan
Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional and therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study, we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue microarray of patient tumors. Tissue microarray immunohistochemistry analysis showed that the overall and five-year survival rates of patients with high levels of PD-L1 expression were significantly shorter than patients with low levels...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413007/a-homozygous-keap1-knockout-human-embryonic-stem-cell-line-generated-using-crispr-cas9-mediates-gene-targeting
#6
So-Jung Kim, Omer Habib, Jin-Soo Kim, Hyo-Won Han, Soo Kyung Koo, Jung-Hyun Kim
Kelch-like ECH-associated protein 1 (keap1) is a cysteine-rich protein that interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to the degradation of Nrf2 (Kim et al., 2014a). Disruption of Keap1 results in the induction of Nrf2-related signaling pathways involving the expression of a set of anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic stem cell (hESC). The Keap1 homozygous-knockout H9 cell line retained normal morphology, gene expression, and in vivo differentiation potential...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28413005/generation-of-a-nrf2-homozygous-knockout-human-embryonic-stem-cell-line-using-crispr-cas9
#7
So-Jung Kim, Omer Habib, Jin-Soo Kim, Hyo-Won Han, Soo Kyung Koo, Jung-Hyun Kim
Nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2) is a well-known transcription factor that regulates the expression of a large number of anti-oxidant genes in mammalian cells (J.H. Kim et al., 2014). Here, we generated a homozygous Nrf2 knockout human embryonic stem cell (hESC) line, H9Nrf2KO-A13, using the CRISPR/Cas9 genome editing method. The Nrf2 homozygous knockout H9 cell line maintains pluripotency, differentiation potential into three germ layers, and a normal karyotype.
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28389661/crispr-cas9-mediated-pd-1-disruption-enhances-anti-tumor-efficacy-of-human-chimeric-antigen-receptor-t-cells
#8
Levi J Rupp, Kathrin Schumann, Kole T Roybal, Rachel E Gate, Chun J Ye, Wendell A Lim, Alexander Marson
Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340349/structure-reveals-mechanisms-of-viral-suppressors-that-intercept-a-crispr-rna-guided-surveillance-complex
#9
Saikat Chowdhury, Joshua Carter, MaryClare F Rollins, Sarah M Golden, Ryan N Jackson, Connor Hoffmann, Lyn'Al Nosaka, Joseph Bondy-Denomy, Karen L Maxwell, Alan R Davidson, Elizabeth R Fischer, Gabriel C Lander, Blake Wiedenheft
Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR-mediated adaptive immune systems for protection from viral infection, and viruses have evolved diverse anti-CRISPR (Acr) proteins that subvert these immune systems. The adaptive immune system in Pseudomonas aeruginosa (type I-F) relies on a 350 kDa CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease for target degradation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the Csy complex bound to two different Acr proteins, AcrF1 and AcrF2, at an average resolution of 3...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28330178/emergence-of-mixed-infection-of-beijing-non-beijing-strains-among-multi-drug-resistant-mycobacterium-tuberculosis-in-pakistan
#10
Samar Mustafa, Hasnain Javed, Jawairia Hashmi, Nazia Jamil, Zarfishan Tahir, Abdul Majeed Akhtar
Tuberculosis (TB) remains as one of the deadliest diseases after HIV globally with 95 % of deaths confined to low-and-middle income countries. Pakistan is fifth among the 22 high-burden TB countries with the incidence rate of 230/100,000 persons, however, studies related to prevalent Mycobacterium tuberculosis strains and their spread, drug resistance pattern and evolutionary genetics are inadequate. The present study was undertaken to highlight the circulation of M. tuberculosis strains causing drug resistant TB in our community by targeting the molecular marker IS6110 and then characterization of these strains as Beijing and Non-Beijing genotypes...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28322797/transcriptional-activation-of-the-mica-gene-with-an-engineered-crispr-cas9-system
#11
Kazuma Sekiba, Mari Yamagami, Motoyuki Otsuka, Tatsunori Suzuki, Takahiro Kishikawa, Rei Ishibashi, Motoko Ohno, Masaya Sato, Kazuhiko Koike
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a prototypical NKG2D ligand. Because immune cells, such as natural killer (NK) cells, recognize virally infected or transformed cells and eliminate them through the interaction between NKG2D receptors on NK cells and NKG2D ligands on pathogenic cells, MICA expression levels are associated with NK cell-mediated immunity. Here, we report that an engineered clustered regularly interspaced short palindromic repeats-Cas9-related complex targeting MICA gene promoter sequences activates transcription of the MICA gene from its endogenous locus...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28247934/anti-crispr-proteins-counterattack-of-phages-on-bacterial-defense-crispr-cas-system
#12
Kulbhushan Chaudhary, Anirudha Chattopadhyay, Dharmendra Pratap
Since the dawn of life there is a never ending strife between bacteria and phages. Both are perpetually changing their strategies to take over each other. CRISPR/Cas is the most widespread defense system used by bacteria against mobile genetic elements (MGEs) such as phages, cojugative palsmids, transoposons and pathogenicity islands. This system utilizes small guide RNA molecules to protect against phages infection and invasion by MGEs. Phages circumvent to these antiviral barriers by point mutation in PAM (protospacer-adjacent motif) sequence, genome rearrangements and by using anti-CRISPR proteins...
March 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28241141/enl-links-histone-acetylation-to-oncogenic-gene-expression-in-acute-myeloid-leukaemia
#13
Liling Wan, Hong Wen, Yuanyuan Li, Jie Lyu, Yuanxin Xi, Takayuki Hoshii, Julia K Joseph, Xiaolu Wang, Yong-Hwee E Loh, Michael A Erb, Amanda L Souza, James E Bradner, Li Shen, Wei Li, Haitao Li, C David Allis, Scott A Armstrong, Xiaobing Shi
Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Recognition of modified histones by 'reader' proteins constitutes a key mechanism underlying these processes; therefore, targeting such pathways holds clinical promise, as exemplified by the development of bromodomain and extra-terminal (BET) inhibitors. We recently identified the YEATS domain as an acetyl-lysine-binding module, but its functional importance in human cancer remains unknown...
March 9, 2017: Nature
https://www.readbyqxmd.com/read/28235822/transient-translational-quiescence-in-primordial-germ-cells
#14
Nathalie Oulhen, S Zachary Swartz, Jessica Laird, Alexandra Mascaro, Gary Wessel
Stem cells in animals often exhibit a slow cell cycle and/or low transcriptional activity referred to as quiescence. Here we report that the translational activity in the primordial germ cells (PGCs) of the sea urchin embryo (Strongylocentrotus purpuratus) is quiescent. We measured new protein synthesis with O-propargyl-puromycin, and L-homopropargylglycine, Click-iT technologies and determined that these cells synthesize protein at only 6% the level of their adjacent somatic cells. Knock-down of translation of the RNA-binding protein Nanos2 by morpholino anti-sense oligonucleotides, or knock-out of the Nanos2 gene by CRISPR/Cas9 resulted in a significant, but partial increase (47%) in general translation specifically in the PGCs...
February 24, 2017: Development
https://www.readbyqxmd.com/read/28231254/rapid-generation-of-drug-resistance-alleles-at-endogenous-loci-using-crispr-cas9-indel-mutagenesis
#15
Jonathan J Ipsaro, Chen Shen, Eri Arai, Yali Xu, Justin B Kinney, Leemor Joshua-Tor, Christopher R Vakoc, Junwei Shi
Genetic alterations conferring resistance to the effects of chemical inhibitors are valuable tools for validating on-target effects in cells. Unfortunately, for many therapeutic targets such alleles are not available. To address this issue, we evaluated whether CRISPR-Cas9-mediated insertion/deletion (indel) mutagenesis can produce drug-resistance alleles at endogenous loci. This method takes advantage of the heterogeneous in-frame alleles produced following Cas9-mediated DNA cleavage, which we show can generate rare alleles that confer resistance to the growth-arrest caused by chemical inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28228588/investigation-of-the-role-of-protein-kinase-d-in-human-rhinovirus-replication
#16
Anabel Guedán, Dawid Swieboda, Mark Charles, Marie Toussaint, Sebastian L Johnston, Amin Asfor, Anusha Panjwani, Tobias J Tuthill, Henry Danahay, Tony Raynham, Aurelie Mousnier, Roberto Solari
Picornavirus replication is known to cause extensive remodelling of Golgi and endoplasmic reticulum membranes and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi vesicular and lipid transport, we hypothesised that PKD played a role in viral replication...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28215705/kras-allelic-imbalance-enhances-fitness-and-modulates-map-kinase-dependence-in-cancer
#17
Michael R Burgess, Eugene Hwang, Rana Mroue, Craig M Bielski, Anica M Wandler, Benjamin J Huang, Ari J Firestone, Amy Young, Jennifer A Lacap, Lisa Crocker, Saurabh Asthana, Elizabeth M Davis, Jin Xu, Keiko Akagi, Michelle M Le Beau, Qing Li, Benjamin Haley, David Stokoe, Deepak Sampath, Barry S Taylor, Marie Evangelista, Kevin Shannon
Investigating therapeutic "outliers" that show exceptional responses to anti-cancer treatment can uncover biomarkers of drug sensitivity. We performed preclinical trials investigating primary murine acute myeloid leukemias (AMLs) generated by retroviral insertional mutagenesis in Kras(G12D) "knockin" mice with the MEK inhibitor PD0325901 (PD901). One outlier AML responded and exhibited intrinsic drug resistance at relapse. Loss of wild-type (WT) Kras enhanced the fitness of the dominant clone and rendered it sensitive to MEK inhibition...
February 23, 2017: Cell
https://www.readbyqxmd.com/read/28196870/biallelic-insertion-of-a-transcriptional-terminator-via-the-crispr-cas9-system-efficiently-silences-expression-of-protein-coding-and-non-coding-rna-genes
#18
Yangyang Liu, Xiao Han, Junting Yuan, Tuoyu Geng, Shihao Chen, Xuming Hu, Isabelle H Cui, Hengmi Cui
The type II bacterial CRISPR/Cas9 system is a simple, convenient, and powerful tool for targeted gene editing. Here, we describe a CRISPR/Cas9-based approach for inserting a poly(A) transcriptional terminator into both alleles of a targeted gene to silence protein-coding and non-protein-coding genes, which often play key roles in gene regulation but are difficult to silence via insertion or deletion of short DNA fragments. The integration of 225 bp of bovine growth hormone poly(A) signals into either the first intron or the first exon or behind the promoter of target genes caused efficient termination of expression of PPP1R12C, NSUN2 (protein-coding genes), and MALAT1 (non-protein-coding gene)...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28159786/evolution-of-pectobacterium-bacteriophage-%C3%AE-m1-to-escape-two-bifunctional-type-iii-toxin-antitoxin-and-abortive-infection-systems-through-mutations-in-a-single-viral-gene
#19
Tim R Blower, Ray Chai, Rita Przybilski, Shahzad Chindhy, Xinzhe Fang, Samuel E Kidman, Hui Tan, Ben F Luisi, Peter C Fineran, George P C Salmond
Some bacteria, when infected by their viral parasites (bacteriophages), undergo a suicidal response that also terminates productive viral replication (abortive infection [Abi]). This response can be viewed as an altruistic act protecting the uninfected bacterial clonal population. Abortive infection can occur through the action of type III protein-RNA toxin-antitoxin (TA) systems, such as ToxINPa from the phytopathogen Pectobacterium atrosepticum Rare spontaneous mutants evolved in the generalized transducing phage ΦM1, which escaped ToxINPa-mediated abortive infection in P...
April 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28148555/targeting-toxoplasma-gondii-cpsf3-as-a-new-approach-to-control-toxoplasmosis
#20
Andrés Palencia, Alexandre Bougdour, Marie-Pierre Brenier-Pinchart, Bastien Touquet, Rose-Laurence Bertini, Cristina Sensi, Gabrielle Gay, Julien Vollaire, Véronique Josserand, Eric Easom, Yvonne R Freund, Hervé Pelloux, Philip J Rosenthal, Stephen Cusack, Mohamed-Ali Hakimi
Toxoplasma gondii is an important food and waterborne pathogen causing toxoplasmosis, a potentially severe disease in immunocompromised or congenitally infected humans. Available therapeutic agents are limited by suboptimal efficacy and frequent side effects that can lead to treatment discontinuation. Here we report that the benzoxaborole AN3661 had potent in vitro activity against T. gondii Parasites selected to be resistant to AN3661 had mutations in TgCPSF3, which encodes a homologue of cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3), an endonuclease involved in mRNA processing in eukaryotes...
March 2017: EMBO Molecular Medicine
keyword
keyword
108020
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"