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https://www.readbyqxmd.com/read/28030561/drosophila-ddx3-belle-exerts-its-function-outside-of-the-wnt-wingless-signaling-pathway
#1
Fabian H Jenny, Konrad Basler
The helicases human DDX3 and Drosophila Belle (Bel) are part of a well-defined subfamily of the DEAD-box helicases. Individual subfamily-members perform a myriad of functions in nuclear and cytosolic RNA metabolism. It has also been reported that DDX3X is involved in cell signaling, including IFN-α and IFN-β inducing pathways upon viral infection as well as in Wnt signaling. Here we used a collection of EMS-induced bel alleles recovered from a Wingless (Wg) suppressor screen to analyze the role of the Drosophila homolog of DDX3 in Wg/Wnt signaling...
2016: PloS One
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#2
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27999982/the-prognostic-effect-of-ddx3-upregulation-in-distant-breast-cancer-metastases
#3
Marise R Heerma van Voss, Willemijne A M E Schrijver, Natalie D Ter Hoeve, Laurien D Hoefnagel, Quirine F Manson, Elsken van der Wall, Venu Raman, Paul J van Diest
Metastatic breast cancer remains one of the leading causes of death in women and identification of novel treatment targets is therefore warranted. Functional studies showed that the RNA helicase DDX3 promotes metastasis, but DDX3 expression was never studied in patient samples of metastatic cancer. In order to validate previous functional studies and to evaluate DDX3 as a potential therapeutic target, we investigated DDX3 expression in paired samples of primary and metastatic breast cancer. Samples from 79 breast cancer patients with distant metastases at various anatomical sites were immunohistochemically stained for DDX3...
December 20, 2016: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/27980081/ddx3-directly-regulates-traf3-ubiquitination-and-acts-as-a-scaffold-to-coordinate-assembly-of-signalling-complexes-downstream-of-mavs
#4
Lili Gu, Anthony Fullam, Niamh McCormack, Yvette Hoehn, Martina Schroeder
Human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IκB-kinase-ε (IKKε), the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination...
December 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27736973/the-dead-box-rna-helicase-ddx3-interacts-with-nf-%C3%AE%C2%BAb-subunit-p65-and-suppresses-p65-mediated-transcription
#5
Nian Xiang, Miao He, Musarat Ishaq, Yu Gao, Feifei Song, Liang Guo, Li Ma, Guihong Sun, Dan Liu, Deyin Guo, Yu Chen
RNA helicase family members exhibit diverse cellular functions, including in transcription, pre-mRNA processing, RNA decay, ribosome biogenesis, RNA export and translation. The RNA helicase DEAD-box family member DDX3 has been characterized as a tumour-associated factor and a transcriptional co-activator/regulator. Here, we demonstrate that DDX3 interacts with the nuclear factor (NF)-κB subunit p65 and suppresses NF-κB (p65/p50)-mediated transcriptional activity. The downregulation of DDX3 by RNA interference induces the upregulation of NF-κB (p65/p50)-mediated transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27735940/ddx3-dead-box-rna-helicase-plays-a-central-role-in-mitochondrial-protein-quality-control-in-leishmania
#6
Prasad Kottayil Padmanabhan, Ouafa Zghidi-Abouzid, Mukesh Samant, Carole Dumas, Bruno Guedes Aguiar, Jerome Estaquier, Barbara Papadopoulou
DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads to the accumulation of mitochondrial reactive oxygen species (ROS) associated with a defect in hydrogen peroxide detoxification. Upon stress, ROS production is greatly enhanced, causing mitochondrial membrane potential loss, mitochondrial fragmentation, and cell death...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27634756/rk-33-radiosensitizes-prostate-cancer-cells-by-blocking-the-rna-helicase-ddx3
#7
Min Xie, Farhad Vesuna, Saritha Tantravedi, Guus M Bol, Marise R Heerma van Voss, Katriana Nugent, Reem Malek, Kathleen Gabrielson, Paul J van Diest, Phuoc T Tran, Venu Raman
Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27572922/c-terminal-residues-specific-to-vasa-among-dead-box-helicases-are-required-for-its-functions-in-pirna-biogenesis-and-embryonic-patterning
#8
Mehrnoush Dehghani, Paul Lasko
The DEAD-box RNA helicase Vasa (Vas, also known as DDX4) is required for germ cell development. In Drosophila, analysis of hypomorphic mutations has implicated maternally expressed Vas in germ cell formation and posterior embryonic patterning. vas-null females, which rarely complete oogenesis, exhibit defects in mitotic progression of germline stem cells, Piwi-interacting RNA (piRNA)-mediated transposon silencing, and translation of Gurken (Grk), an EGFR ligand. The carboxy-terminal region of Vas orthologs throughout the animal kingdom consists of several acidic residues as well as an invariant tryptophan in the penultimate or ultimate position (Trp660 in Drosophila melanogaster)...
August 29, 2016: Development Genes and Evolution
https://www.readbyqxmd.com/read/27344963/ddx3-represses-stemness-by-epigenetically-modulating-tumor-suppressive-mirnas-in-hepatocellular-carcinoma
#9
Hao-Kang Li, Ru-Tsun Mai, Hsien-Da Huang, Chih-Hung Chou, Yi-An Chang, Yao-Wen Chang, Li-Ru You, Chun-Ming Chen, Yan-Hwa Wu Lee
Studies indicate that the presence of cancer stem cells (CSCs) is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, the functional role of DDX3 in regulation of hepatic CSCs was investigated. Our results demonstrated that reduced DDX3 expression was not only inversely associated with tumor grade, but also predicted poor prognosis of HCC patients. Knockdown of DDX3 in HCC cell line HepG2 induced stemness gene signature followed by occurrence of self-renewal, chemoreisistance, EMT, migration as well as CSC expansion, and most importantly, DDX3 knockdown promotes tumorigenesis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27300509/immunosuppressive-yersinia-effector-yopm-binds-dead-box-helicase-ddx3-to-control-ribosomal-s6-kinase-in-the-nucleus-of-host-cells
#10
Laura Berneking, Marie Schnapp, Andreas Rumm, Claudia Trasak, Klaus Ruckdeschel, Malik Alawi, Adam Grundhoff, Alexey G Kikhney, Friedrich Koch-Nolte, Friedrich Buck, Markus Perbandt, Christian Betzel, Dmitri I Svergun, Moritz Hentschke, Martin Aepfelbacher
Yersinia outer protein M (YopM) is a crucial immunosuppressive effector of the plaque agent Yersinia pestis and other pathogenic Yersinia species. YopM enters the nucleus of host cells but neither the mechanisms governing its nucleocytoplasmic shuttling nor its intranuclear activities are known. Here we identify the DEAD-box helicase 3 (DDX3) as a novel interaction partner of Y. enterocolitica YopM and present the three-dimensional structure of a YopM:DDX3 complex. Knockdown of DDX3 or inhibition of the exportin chromosomal maintenance 1 (CRM1) increased the nuclear level of YopM suggesting that YopM exploits DDX3 to exit the nucleus via the CRM1 export pathway...
June 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27252702/accessory-factors-of-cytoplasmic-viral-rna-sensors-required-for-antiviral-innate-immune-response
#11
REVIEW
Hiroyuki Oshiumi, Takahisa Kouwaki, Tsukasa Seya
Type I interferon (IFN) induces many antiviral factors in host cells. RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27186411/multifunctional-ddx3-dual-roles-in-various-cancer-development-and-its-related-signaling-pathways
#12
REVIEW
Luqing Zhao, Yitao Mao, Jianhua Zhou, Yuelong Zhao, Ya Cao, Xiang Chen
DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box protein, which is a cluster of ATP-dependent and the largest family of RNA helicase. DEAD-box family is characterized by the regulation of ATPase and helicase activities, the modulation of RNA metabolism, and the actors of RNA binding proteins or molecular chaperones to interact with other proteins or RNA. For DDX3, it exerts its multifaceted roles in viral manipulation, stress response, hypoxia, radiation response and apoptosis, and is closely related to cancer development and progression...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27179789/targeted-inactivation-of-murine-ddx3x-essential-roles-of-ddx3x-in-placentation-and-embryogenesis
#13
Chia-Yu Chen, Chieh-Hsiang Chan, Chun-Ming Chen, Yin-Shuan Tsai, Tsung-Yuan Tsai, Yan-Hwa Wu Lee, Li-Ru You
The X-linked DEAD-box RNA helicase DDX3 (DDX3X) is a multifunctional protein that has been implicated in gene regulation, cell cycle control, apoptosis, and tumorigenesis. However, the precise physiological function of Ddx3x during development remains unknown. Here, we show that loss of Ddx3x results in an early post-implantation lethality in male mice. The size of the epiblast marked by Oct3/4 is dramatically reduced in embryonic day 6.5 (E6.5) Ddx3x(-)/Y embryos. Preferential paternal X chromosome inactivation (XCI) in extraembryonic tissues of Ddx3x heterozygous (Ddx3x(-/+)) female mice with a maternally inherited null allele leads to placental abnormalities and embryonic lethality during development...
May 14, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27118832/human-ddx3-protein-is-a-valuable-target-to-develop-broad-spectrum-antiviral-agents
#14
Annalaura Brai, Roberta Fazi, Cristina Tintori, Claudio Zamperini, Francesca Bugli, Maurizio Sanguinetti, Egidio Stigliano, José Esté, Roger Badia, Sandra Franco, Miguel A Martinez, Javier P Martinez, Andreas Meyerhans, Francesco Saladini, Maurizio Zazzi, Anna Garbelli, Giovanni Maga, Maurizio Botta
Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus...
May 10, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27105836/venezuelan-equine-encephalitis-virus-non-structural-protein-3-nsp3-interacts-with-rna-helicases-ddx1-and-ddx3-in-infected-cells
#15
Moushimi Amaya, Taryn Brooks-Faulconer, Tyler Lark, Forrest Keck, Charles Bailey, Venu Raman, Aarthi Narayanan
The mosquito-borne New World alphavirus, Venezuelan equine encephalitis virus (VEEV) is a Category B select agent with no approved vaccines or therapies to treat infected humans. Therefore it is imperative to identify novel targets that can be targeted for effective therapeutic intervention. We aimed to identify and validate interactions of VEEV nonstructural protein 3 (nsP3) with host proteins and determine the consequences of these interactions to viral multiplication. We used a HA tagged nsP3 infectious clone (rTC-83-nsP3-HA) to identify and validate two RNA helicases: DDX1 and DDX3 that interacted with VEEV-nsP3...
July 2016: Antiviral Research
https://www.readbyqxmd.com/read/27090004/protein-protein-interaction-analysis-for-functional-characterization-of-helicases
#16
REVIEW
Boris L Zybailov, Alicia K Byrd, Galina V Glazko, Yasir Rahmatallah, Kevin D Raney
Helicases are enzymes involved in nucleic acid metabolism, playing major roles in replication, transcription, and repair. Defining helicases oligomerization state and transient and persistent protein interactions is essential for understanding of their function. In this article we review current methods for the protein-protein interaction analysis, and discuss examples of its application to the study of helicases: Pif1 and DDX3. Proteomics methods are our main focus - affinity pull-downs and chemical cross-linking followed by mass spectrometry...
October 1, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27058758/medulloblastoma-associated-ddx3-variant-selectively-alters-the-translational-response-to-stress
#17
Sekyung Oh, Ryan A Flynn, Stephen N Floor, James Purzner, Lance Martin, Brian T Do, Simone Schubert, Dedeepya Vaka, Sorana Morrissy, Yisu Li, Marcel Kool, Volker Hovestadt, David T W Jones, Paul A Northcott, Thomas Risch, Hans-Jörg Warnatz, Marie-Laure Yaspo, Christopher M Adams, Ryan D Leib, Marcus Breese, Marco A Marra, David Malkin, Peter Lichter, Jennifer A Doudna, Stefan M Pfister, Michael D Taylor, Howard Y Chang, Yoon-Jae Cho
DDX3X encodes a DEAD-box family RNA helicase (DDX3) commonly mutated in medulloblastoma, a highly aggressive cerebellar tumor affecting both children and adults. Despite being implicated in several facets of RNA metabolism, the nature and scope of DDX3's interactions with RNA remain unclear. Here, we show DDX3 collaborates extensively with the translation initiation machinery through direct binding to 5'UTRs of nearly all coding RNAs, specific sites on the 18S rRNA, and multiple components of the translation initiation complex...
May 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27030674/staufen1-impairs-stress-granule-formation-in-skeletal-muscle-cells-from-myotonic-dystrophy-type-1-patients
#18
Aymeric Ravel-Chapuis, Amanda Klein Gunnewiek, Guy Bélanger, Tara E Crawford Parks, Jocelyn Côté, Bernard J Jasmin
Myotonic dystrophy (DM1) is caused by an expansion of CUG repeats (CUG(exp)) in the DMPK mRNA 3'UTR. CUG(exp)-containing mRNAs become toxic to cells by misregulating RNA-binding proteins. Here we investigated the consequence of this RNA toxicity on the cellular stress response. We report that cell stress efficiently triggers formation of stress granules (SGs) in proliferating, quiescent, and differentiated muscle cells, as shown by the appearance of distinct cytoplasmic TIA-1- and DDX3-containing foci. We show that Staufen1 is also dynamically recruited into these granules...
June 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27012366/dead-box-rna-helicase-ddx3-connects-crm1-dependent-nuclear-export-and-translation-of-the-hiv-1-unspliced-mrna-through-its-n-terminal-domain
#19
Alvaro Fröhlich, Bárbara Rojas-Araya, Camila Pereira-Montecinos, Alessandra Dellarossa, Daniela Toro-Ascuy, Yara Prades-Pérez, Francisco García-de-Gracia, Andrea Garcés-Alday, Paulina S Rubilar, Fernando Valiente-Echeverría, Théophile Ohlmann, Ricardo Soto-Rifo
DEAD-box RNA helicase DDX3 is a host factor essential for HIV-1 replication and thus, a potential target for novel therapies aimed to overcome viral resistance. Previous studies have shown that DDX3 promotes nuclear export and translation of the HIV-1 unspliced mRNA. Although the function of DDX3 during both processes requires its catalytic activity, it is unknown whether other domains surrounding the helicase core are involved. Here, we show the involvement of the N- and C-terminal domains of DDX3 in the regulation of HIV-1 unspliced mRNA translation...
May 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27007150/ddx3-enhances-oncogenic-kras%C3%A2-induced-tumor-invasion-in-colorectal-cancer-via-the-%C3%AE-%C3%A2-catenin-zeb1-axis
#20
De-Wei Wu, Po-Lin Lin, Ya-Wen Cheng, Chi-Chou Huang, Lee Wang, Huei Lee
DDX3 plays a dual role in colorectal cancer; however, the role and underlying mechanism of DDX3 in colorectal tumorigenesis remains unclear. Here, we provide evidence that DDX3 enhances oncogenic KRAS transcription via an increase in SP1 binding to its promoter. Accelerating oncogenic KRAS expression by DDX3 promotes the invasion capability via the ERK/PTEN/AKT/β-catenin cascade. Moreover, the β-catenin/ZEB1 axis is responsible for DDX3-induced cell invasiveness and xenograft lung tumor nodule formation. The xenograft lung tumor nodules induced by DDX3-overexpressing T84 stable clone were nearly suppressed by the inhibitor of AKT (perifosine) or β-catenin (XAV939)...
April 19, 2016: Oncotarget
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