Abstract:
:Cytosolic RNA/DNA sensing elicits primary defense against viral pathogens. Interferon regulatory factor 3 (IRF3), a key signal mediator/transcriptional factor of the antiviral-sensing pathway, is indispensible for interferon production and antiviral defense. However, how the status of IRF3 activation is controlled remains elusive. Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1 (Mst1), but not Mst2, profoundly inhibited cytosolic nucleic acid sensing. Mst1 associated with IRF3 and directly phosphorylated IRF3 at Thr75 and Thr253. This Mst1-mediated phosphorylation abolished activated IRF3 homodimerization, its occupancy on chromatin, and subsequent IRF3-mediated transcriptional responses. In addition, Mst1 also impeded virus-induced activation of TANK-binding kinase 1 (TBK1), further attenuating IRF3 activation. As a result, Mst1 depletion or ablation enabled an enhanced antiviral response and defense in cells and mice. Therefore, the identification of Mst1 as a novel physiological negative regulator of IRF3 activation provides mechanistic insights into innate antiviral defense and potential antiviral prevention strategies.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Meng F,Zhou R,Wu S,Zhang Q,Jin Q,Zhou Y,Plouffe SW,Liu S,Song H,Xia Z,Zhao B,Ye S,Feng XH,Guan KL,Zou J,Xu Pdoi
10.1101/gad.277533.116subject
Has Abstractpub_date
2016-05-01 00:00:00pages
1086-100issue
9eissn
0890-9369issn
1549-5477pii
gad.277533.116journal_volume
30pub_type
杂志文章abstract::The ascidian tadpole represents the most simplified chordate body plan. It contains a notochord composed of just 40 cells, but as in vertebrates Brachyury is essential for notochord differentiation. Here, we show that the misexpression of the Brachyury gene (Ci-Bra) of Ciona intestinalis is sufficient to transform end...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.12.1519
更新日期:1999-06-15 00:00:00
abstract::Eukaryotic translation initiation begins with ribosomal recruitment of aminoacylated initiator tRNA (Met-tRNA(Met)(i)) by eukaryotic initiation factor eIF2. In cooperation with eIF3, eIF1, and eIF1A, Met-tRNA(Met)(i)/eIF2/GTP binds to 40S subunits yielding 43S preinitiation complexes that attach to the 5'-terminal reg...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1957510
更新日期:2010-08-15 00:00:00
abstract::The association of proteins with the branch site region during pre-mRNA splicing was probed using a novel methodology to site-specifically modify the pre-mRNA with the photo-reagent benzophenone. Three sets of proteins were distinguished by the kinetics of their associations with pre-mRNAs, by their association with d...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.24.3008
更新日期:1994-12-15 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%-5%. The cancer's lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biol...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1415606
更新日期:2006-05-15 00:00:00
abstract::Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.943001
更新日期:2001-12-15 00:00:00
abstract::Heparan sulfate proteoglycans have been implicated in the presentation of a number of secreted signaling molecules to their signal-transducing receptors. We have characterized a gene trap mutation in the gene encoding a heparan sulfate biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice we...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.12.1894
更新日期:1998-06-15 00:00:00
abstract::Although branchpoint recognition is an essential component of intron excision during the RNA splicing process, the branchpoint itself is frequently assumed to be a basal, rather than regulatory, sequence feature. However, this assumption has not been systematically tested due to the technical difficulty of identifying...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.312058.118
更新日期:2018-04-01 00:00:00
abstract::The regulation of gene transcription is critical for the proper development and growth of an organism. The transcription of protein-coding genes initiates at the RNA polymerase II core promoter, which is a diverse module that can be controlled by many different elements such as the TATA box and downstream core promote...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1698108
更新日期:2008-10-15 00:00:00
abstract::Pcf11 is one of numerous proteins involved in pre-mRNA 3'-end processing and transcription termination. Using elongation complexes (ECs) formed from purified yeast RNA polymerase II (Pol II), we show that a 140-amino acid polypeptide from yeast Pcf11 is capable of dismantling the EC in vitro. This action depends on th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1296305
更新日期:2005-07-01 00:00:00
abstract::Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302679.117
更新日期:2017-08-15 00:00:00
abstract::The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.375206
更新日期:2006-07-01 00:00:00
abstract::The gamma delta T-cell receptor (TCR) is the first TCR to be expressed in ontogeny in all vertebrates in which it has been examined thoroughly. Murine gamma delta cell-surface protein is detected by the fourteenth day of gestation. In this work, the activation of gamma delta RNA has been studied. Data indicate that th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.8.1304
更新日期:1990-08-01 00:00:00
abstract::The incretin hormone GLP1 promotes islet-cell survival via the second messenger cAMP. Here we show that mice deficient in the activity of CREB, caused by expression of a dominant-negative A-CREB transgene in pancreatic beta-cells, develop diabetes secondary to beta-cell apoptosis. Remarkably, A-CREB severely disrupted...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1097103
更新日期:2003-07-01 00:00:00
abstract::Members of the metazoan nuclear receptor superfamily regulate gene expression programs in response to binding of cognate lipophilic ligands. Evolutionary studies using bioinformatics tools have concluded that lower eukaryotes, such as fungi, lack nuclear receptor homologs. Here we review recent discoveries suggesting ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1743009
更新日期:2009-02-15 00:00:00
abstract::cappuccino and spire are unique Drosophila maternal-effect loci that participate in pattern formation in both the anteroposterior and dorsoventral axes of the early embryo. Mutant females produce embryos lacking pole cells, polar granules, and normal abdominal segmentation. They share these defects with the posterior ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1437
更新日期:1989-09-01 00:00:00
abstract::In Drosophila germ cells, PIWI-interacting RNAs (piRNAs) are amplified through a PIWI slicer-dependent feed-forward loop termed the ping-pong cycle, yielding secondary piRNAs. However, the detailed mechanism remains poorly understood, largely because an ex vivo model system amenable to biochemical analyses has not bee...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.283929.116
更新日期:2016-07-15 00:00:00
abstract::Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.173922.111
更新日期:2011-11-01 00:00:00
abstract::Signal transduction through the FGF receptor is essential for the specification of the vertebrate body plan. Blocking the FGF pathway in early Xenopus embryos inhibits mesoderm induction and results in truncation of the anterior-posterior axis. The Drosophila gene sprouty encodes an antagonist of FGF signaling, which ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.191301
更新日期:2001-05-01 00:00:00
abstract::To identify regions of the largest subunit of RNA polymerase that are potentially involved in transcript elongation and termination, we have characterized amino acid substitutions in the beta' subunit of Escherichia coli RNA polymerase that alter expression of reporter genes preceded by terminators in vivo. Terminatio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.23.2913
更新日期:1994-12-01 00:00:00
abstract::Placental development is profoundly influenced by oxygen (O(2)) tension. Human cytotrophoblasts proliferate in vitro under low O(2) conditions but differentiate at higher O(2) levels, mimicking the developmental transition they undergo as they invade the placental bed to establish the maternal-fetal circulation in viv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.853700
更新日期:2000-12-15 00:00:00
abstract::We have developed a simple, effective genetic screen for mutant alleles of eukaryotic DNA topoisomerase I that manifest severely depressed or complete loss of enzymatic function. The screen is based on the extreme toxicity of vaccinia topoisomerase expression in the Escherichia coli lysogen strain BL21(DE3) and is not...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.515
更新日期:1990-04-01 00:00:00
abstract::The growth suppression function of the retinoblastoma protein (RB) is mediated by its interaction with a variety of cellular proteins. RB contains at least two protein-binding pockets: the large A/B pocket, which interacts with E2F and the D-type cyclins, and the C pocket, which interacts with the nuclear c-Abl tyrosi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.1.31
更新日期:1995-01-01 00:00:00
abstract::The Tat protein of human immunodeficiency virus type 1 (HIV-1) activates transcription following binding to nascent trans-activation response (TAR) RNA downstream of the transcription start site. Because Tat functions when bound to RNA, and in a position-dependent manner, it has been proposed that Tat works by a novel...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.12b.2496
更新日期:1991-12-01 00:00:00
abstract::The empty spiracles (ems) homeo box gene is required for the development of the Drosophila larval filzkörper, which are structural specializations of the eighth abdominal segment. Filzkörper development is also dependent on the function of the homeotic selector gene Abdominal-B (Abd-B). Here, we show that ems is a dow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.2.229
更新日期:1993-02-01 00:00:00
abstract::Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients' death in early adulthood. CSA and CSB act in a transcription-coupled repair (TCR) pathway, but their functional relationship is not understood. We have previously shown that CSA is a subun...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.378206
更新日期:2006-06-01 00:00:00
abstract::Cdc42p, a Rho-related GTP-binding protein, regulates cytoskeletal polarization and rearrangements in eukaryotic cells, but the effectors mediating this control remain unknown. Through the use of the complete yeast genomic sequence, we have identified two novel Cdc42p targets, Gic1p and Gic2p, which contain consensus C...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.22.2972
更新日期:1997-11-15 00:00:00
abstract::To investigate functional differences between RNA polymerases IIA and IIO (Pol IIA and Pol IIO), with hypo- and hyperphosphorylated carboxy-terminal repeat domains (CTDs), respectively, we have visualized the in vivo distributions of the differentially phosphorylated forms of Pol II on Drosophila polytene chromosomes....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.12a.2329
更新日期:1993-12-01 00:00:00
abstract::In Drosophila, the development of the compound eye depends on the movement of a morphogenetic furrow (MF) from the posterior (P) to the anterior (A) of the eye imaginal disc. We define several subdomains along the A-P axis of the eye disc that express distinct combinations of transcription factors. One subdomain, ante...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1009002
更新日期:2002-09-15 00:00:00
abstract::Somatic cell clones often fail at a developmental stage coincident with commencement of differentiation. The transcription factor Oct4 is expressed during cleavage stages and is essential for the differentiation of the blastocyst. Oct4 expression becomes restricted to the inner cell mass and epiblast. After gastrulati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.966002
更新日期:2002-05-15 00:00:00
abstract::Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271353.115
更新日期:2015-12-01 00:00:00