A5009824810- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Virology and Viral Diseases
- Viral Infections and Vectors
- Virus-based gene therapy research
- RNA Research and Splicing
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- RNA regulation and disease
- vaccines and immunoinformatics approaches
- Cancer Immunotherapy and Biomarkers
- Protein Tyrosine Phosphatases
- NF-κB Signaling Pathways
- Cancer-related molecular mechanisms research
- Inflammasome and immune disorders
- Influenza Virus Research Studies
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Respiratory viral infections research
- Melanoma and MAPK Pathways
- Viral Infections and Immunology Research
- Mosquito-borne diseases and control
- MicroRNA in disease regulation
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
Northwestern University
2013-2023
Evanston Hospital
2013
NorthShore University HealthSystem
2004-2009
Palmetto Hematology Oncology
2009
Icahn School of Medicine at Mount Sinai
2000-2006
Australian Centre for Disease Preparedness
2003
Commonwealth Scientific and Industrial Research Organisation
2003
Beth Israel Deaconess Medical Center
2000
Harvard University
2000
Rockefeller University
1994-1999
Stat3 activation has been associated with cytokine-induced proliferation, anti-apoptosis, and transformation. Constitutively activated found in many human tumors as well v-abl- v-src-transformed cell lines. Because of these correlations, we examined directly the relationship to cellular transformation that wild-type enhances transforming potential v-src while three dominant negative mutants inhibit v-srctransformation. or mutant proteins did not affect v-ras We conclude a necessary role
ABSTRACT We present a novel mechanism by which viruses may inhibit the alpha/beta interferon (IFN-α/β) cascade. The double-stranded RNA (dsRNA) binding protein NS1 of influenza virus is shown to prevent potent antiviral response inhibiting activation regulatory factor 3 (IRF-3), key regulator IFN-α/β gene expression. IRF-3 and, as consequence, IFN-β mRNA induction are inhibited in wild-type (PR8) virus-infected cells but not infected with an isogenic lacking (delNS1 virus). Furthermore, be...
Stat1 and Stat3 are two members of the ligand-activated transcription factor family that serve dual functions signal transducers activators transcription. Whereas proteins select very similar (not identical) optimum binding sites from random oligonucleotides, differences in their affinity were readily apparent with natural STAT-binding sites. To take advantage these different affinities, chimeric Stat1:Stat3 molecules used to locate amino acids could discriminate a general site specific...
Type I (alpha, beta) and type II (gamma) interferons (IFNs) can restrict the growth of many cell types. INF-stimulated gene transcription, a key early event in IFN response, acts through Janus kinase-signal transducers activators transcription pathway, which both IFN-alpha IFN-gamma activate factor Stat1. A line lacking Stat1 (U3A) was not growth-arrested by or IFN-gamma, experiments were carried out with U3A cells permanently expressing normal various mutant forms protein. Only complete...
Signal transducers and activators of transcription (STATs) enhance specific genes in response to cytokines growth factors. STAT1 is also required for efficient constitutive expression the caspases Ice, Cpp32, Ich-1 human fibroblasts. As a consequence, STAT1-null cells are resistant apoptosis by tumor necrosis factor alpha (TNF-alpha). Reintroduction STAT1alpha restored both TNF-alpha-induced Ich-1. Variant proteins carrying point mutations that inactivate domains STAT dimer formation...
Interferon γ (IFN-γ) induces rapid tyrosine phosphorylation of the latent cytoplasmic transcription factor, Stat1, which then forms homodimers, translocates to nucleus and participates in IFN-γ-induced transcription. However, little is known interactions between Stat1 general machinery during transcriptional activation. We show here that can directly interact with CREB-binding protein (CBP)/p300 family coactivators. Specifically, two interaction regions were identified: amino-terminal region...
STAT transcription factors are expressed in many cell types and bind to similar sequences. However, different gene knock-outs show very distinct phenotypes. To determine whether differences between the binding specificities of proteins account for these effects, we compared sequences bound by STAT1, STAT5A, STAT5B, STAT6. One sequence set was selected from random oligonucleotides recombinant or For another including weak sites, quantified relative affinities We results sites natural target...
ABSTRACT Antiviral innate immune responses can be triggered by accumulation of intracellular nucleic acids resulting from virus infections. Double-stranded RNA (dsRNA) detected the cytoplasmic helicase proteins RIG-I and MDA5, two that share sequence similarities within a caspase recruitment domain (CARD) DExD/H box domain. These are considered dsRNA sensors thought to transmit signal mitochondrial adapter, IPS-1 (also known as MAVS, VISA, or CARDIF) via CARD interactions. coordinates...
Characterization of recent outbreaks fatal encephalitis in southeast Asia identified the causative agent to be a previously unrecognized enveloped negative-strand RNA virus Paramyxoviridae family, Nipah virus. One feature linking this family is conserved cysteine-rich domain that hallmark paramyxovirus V proteins. The proteins other species have been linked with evasion host cell interferon (IFN) signal transduction and subsequent antiviral responses by inducing proteasomal degradation...
ABSTRACT Measles virus, a paramyxovirus of the Morbillivirus genus, is responsible for an acute childhood illness that infects over 40 million people and leads to deaths more than 1 annually (C. J. Murray A. D. Lopez, Lancet 349:1269-1276, 1997). virus infection characterized by virus-induced immune suppression creates susceptibility opportunistic infections. Here we demonstrate measles can inhibit cytokine responses direct interference with host STAT protein-dependent signaling systems....
The use of histone deacetylase (HDAC) inhibitors has revealed an essential role for deacetylation in transcription IFN-responsive genes. HDAC1 protein associates with both signal transducer and activator (STAT) 1 STAT2, IFN-α stimulation induces H4. Inhibition by small interfering RNA (siRNA) decreases responsiveness whereas expression augments the response, demonstrating that modulates IFN-α-induced transcription. Importantly, innate antiviral response is inhibited absence activity....
Independent but closely spaced DNA binding sites for Stat3 and c-Jun are required maximal enhancer function in a number of genes, including the gene encoding interleukin-6 (IL-6)-induced acute-phase response protein, alpha(2)-macroglobulin. In addition, physical interaction with c-Jun, based on yeast two-hybrid experiments, has been reported. Here we confirm existence an between both vitro, recombinant proteins, vivo, during transient transfection. Using fragments mapped interactive to...