A5053006729- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Cell death mechanisms and regulation
- Blood Coagulation and Thrombosis Mechanisms
- Cytokine Signaling Pathways and Interactions
- Telomeres, Telomerase, and Senescence
- Immunotherapy and Immune Responses
- Hemophilia Treatment and Research
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Cancer Research and Treatments
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Peptidase Inhibition and Analysis
- Multiple Myeloma Research and Treatments
- T-cell and B-cell Immunology
- S100 Proteins and Annexins
- Ubiquitin and proteasome pathways
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- RNA regulation and disease
- Bone Metabolism and Diseases
- Cancer-related Molecular Pathways
- Protease and Inhibitor Mechanisms
University of Naples Federico II
2016-2025
University of Bologna
2022
Federico II University Hospital
2014-2020
National Institutes of Health
1997-2009
Park University
2006
Keck Hospital of USC
2006
Lexington VA Health Care System
2004
University of Regensburg
2004
University of Udine
1994-2004
National Institute of Allergy and Infectious Diseases
1997-2002
NF-κB is a family of related, dimeric transcription factors that are readily activated in cells by signals associated with stress or pathogens. These critical to host defense, as demonstrated previously mice deficient individual subunits NF-κB. We have generated both the p50 and p52 reveal functions may be shared these two highly homologous proteins. now demonstrate unlike respective single knockout mice, p50/p52 double fail generate mature osteoclasts B cells, apparently because defects...
p52 is a subunit of nuclear factor (NF)-kappa B transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member the I kappa family. To determine nonredundant physiologic roles generated mice deficient in p52. Null mutant were impaired their ability generate antibodies T-dependent antigens, consistent absence cell follicles and follicular dendritic networks secondary...
Nuclear factor κB (NF-κB) plays a pivotal role in inflammation, immunity, stress responses, and protection from apoptosis. Canonical activation of NF-κB is dependent on the phosphorylation inhibitory subunit IκBα that mediated by multimeric, high molecular weight complex, called IκB kinase (IKK) complex. This composed two catalytic subunits, IKKα IKKβ, regulatory subunit, NEMO/IKKγ. The latter protein essential for IKKs NF-κB, but its mechanism action not well understood. Here we identified...
APE1/Ref-1 (hereafter, APE1), a DNA repair enzyme and transcriptional coactivator, is vital protein in mammals. Its role controlling cell growth the molecular mechanisms that fine-tune its different cellular functions are still not known. By an unbiased proteomic approach, we have identified characterized several novel APE1 partners which, unexpectedly, include number of proteins involved ribosome biogenesis RNA processing. In particular, interaction between nucleophosmin (NPM1) was...
NF-kappaB is constitutively activated in primary human thyroid tumors, particularly those of anaplastic type. The inhibition activity the carcinoma cell line, FRO, leads to an increased susceptibility chemotherapeutic drug-induced apoptosis and blockage their ability form tumors nude mice. To identify target genes involved cancer, we analyzed secretome conditioned media from parental NF-kappaB-null FRO cells. Proteomic analysis revealed that neutrophil gelatinase-associated lipocalin (NGAL),...
Abstract IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well autoimmune diseases, such rheumatoid arthritis experimental encephalomyelitis animal models. IL-25 a member family cytokines, but has been associated with Th2 responses instead may negatively cross-regulate Th17/IL-17 responses. can initiate an allergic asthma-like inflammation airways, includes recruitment eosinophils, mucus...
Canonical activation of NF-κB is mediated via phosphorylation the inhibitory IκB proteins by kinase complex (IKK). IKK composed a heterodimer catalytic IKKα and IKKβ subunits presumed regulatory protein termed NEMO (NF-κB essential modulator) or IKKγ. NEMO/IKKγ indispensable for IKKs in response to many signals, but its mechanism action remains unclear. Here we identify TANK (TRAF family member-associated activator) as NEMO/IKKγ-interacting yeast two-hybrid analyses. This interaction...
Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes response to these signals invariably involves transcription factors the NF-κB AP-1/ATF families. Activation is thought be mediated primarily via IκB kinases (IKK), whereas that can by stress-activated protein (SAPKs; also named Jun or JNKs). IKKα IKKβ are two catalytic subunits a core IKK complex contains regulatory subunit NEMO (NF-κB essential modulator)/IKKγ. latter...
Micro-RNAs (miRNAs) have been recently involved in the modulation of several biological activities including cancer. Many human tumors show deregulated expression miRNAs targeting oncogenes and/or tumor suppressors, thus identifying as new molecular targets for cancer therapy.Nuclear factor (NF)-kappaB is strongly activated anaplastic thyroid carcinomas (ATCs). Because regulation miRNA under control RNA polymerase II-dependent transcription factors, we stably inactivated NF-kappaB...
Background: Recently, a growing number of novel genetic defects underlying primary immunodeficiencies (PID) have been identified, increasing the PID up to more than 250 well-defined forms. Next-generation sequencing (NGS) technologies and proper filtering strategies greatly contributed this rapid evolution, providing possibility rapidly simultaneously analyze large numbers genes or whole exome. Objective: To evaluate role targeted next-generation exome in diagnosis case series, characterized...
Tumor necrosis factor (TNF) receptor-associated 2 (TRAF2) is an intracellular protein involved in signal transduction from TNF receptor I and II related receptors. TRAF2 required for TNF-induced activation of c-Jun N-terminal kinase/stress-activated kinase (JNK/SAPK), can also mediate NF-κB. Here we have identified the actin-binding Filamin (actin-binding protein-280) as a TRAF2-interacting protein. binds to Ring zinc finger domain TRAF2. Overexpressed inhibits TRAF2-induced JNK/SAPK...
Thyroid cancer includes three types of carcinomas classified as differentiated thyroid (DTC), medullary carcinomas, and undifferentiated (UTC). DTC generally have a good prognosis, but UTC are usually fatal. Consequently, there is need for new effective therapeutic modalities to improve the survival patients. Here we show that NF-κB activated in human neoplasms, particularly carcinomas. cell lines, reproducing vitro different neoplasias, also basal activity resistance drug-induced apoptosis,...
Abstract Purpose: Immunostimulating Toll-like receptor 9 (TLR9) agonists cause antitumor activity interfering also with cancer proliferation and angiogenesis by mechanisms still incompletely understood. We hypothesized that modified TLR9 could impair epidermal growth factor (EGFR) signaling and, this means, greatly enhance EGFR inhibitors effect, acting on both the targeting immunologic arm. Experimental Design: used a novel second-generation, modified, immunomodulatory agonist (IMO), alone...
The aim of this work was to compare the effects on human amniotic membrane freeze-drying and γ-irradiation at doses 10, 20 30 kGy, with freezing. For purpose, nine cytokines (interleukin platelet-derived growth factor-AA, factor-BB, basic fibroblast factor, epidermal transforming factor beta 1, tissue inhibitors metalloproteinase-1, -2, -4) were titrated in 5 different preparations for each 3 membranes included study. In addition, extracellular matrix structure sample assessed by...
Abstract Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, ability to activate DCs is considered a key tool enhance efficacy quality of vaccination. Here we report novel immunomodulatory sulfolipid named β-SQDG18 that prototypes class natural-derived glycolipids able prime human by TLR2/TLR4-independent mechanism trigger an efficient response in vivo . induces maturation DC...
The cytotoxicity of dental monomers has been widely investigated, but the underlying mechanisms have not elucidated. We studied molecular involved in cell death induced by HEMA. In human primary fibroblasts, HEMA a dose-dependent apoptosis that was confirmed activation caspases-8, -9, and -3. found an increase reactive oxygen species (ROS) NF-κB after exposure. Blocking ROS production anti-oxidants had no direct influence on caused HEMA, inhibition increased fraction apoptotic cells....
ABSTRACT The hepatitis C virus (HCV) E2 envelope glycoprotein is crucial for entry into hepatocytes. A conserved region of encompassing amino acids 412 to 423 (epitope I) and containing Trp420, a residue critical entry, recognized by several broadly neutralizing antibodies. Peptides embodying this epitope I sequence adopt β-hairpin conformation when bound monoclonal antibodies (MAbs) AP33 HCV1. We therefore generated new mouse MAbs that were able bind cyclic peptide residues 422 (C-epitope...
Therapy-induced senescence (TIS) is a major cellular response to anticancer therapies. While induction of persistent growth arrest would be desirable outcome in cancer therapy, it has been shown that, unlike normal cells, cells are able evade the cell cycle and resume proliferation, likely contributing tumor relapse. Notably, that escape from TIS acquire plastic, stem cell-like phenotype. The metabolic dependencies have not thoroughly studied. In this study, we show glutamine depletion...