A5058688311- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Congenital heart defects research
- Growth Hormone and Insulin-like Growth Factors
- Kruppel-like factors research
- Protein Kinase Regulation and GTPase Signaling
- NF-κB Signaling Pathways
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Response and Inflammation
- Pancreatic function and diabetes
- Renal and related cancers
- Cytokine Signaling Pathways and Interactions
- Cell Adhesion Molecules Research
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- Genomics, phytochemicals, and oxidative stress
- Retinoids in leukemia and cellular processes
- Pluripotent Stem Cells Research
- Peroxisome Proliferator-Activated Receptors
University of Castilla-La Mancha
2015-2025
Consejo Superior de Investigaciones Científicas
2014-2020
Center for Biomedical Research of La Rioja
2018
University of the Basque Country
2015
United States Food and Drug Administration
1990-2008
Center for Biologics Evaluation and Research
1993-2003
Universidad de Alcalá
1998
Georgetown University
1991-1994
Georgetown University Medical Center
1993-1994
Institut des Sciences Biologiques
1987-1992
M17885, EMBL accession nos X15267 and X1509636B4 is a human cDNA clone originally isolated by the group of P.Chambon (1) in 1982, from differential library estradiol stimulated versus non MCF-7 breast cancer cells.Because 36B4 mRNA levels are not modified treatment, this probe widely used as control RNAse protection experiments to study regulation transcription several genes.So far, identity was unknown.In an attempt identify 36B4, partial sequencing Pstl-PstI fragment subcloned plasmid pGEM...
Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional protein belonging to the serpin superfamily with demonstrable neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We have previously provided biochemical evidence for high affinity PEDF-binding sites proteins in plasma membranes of retina, retinoblastoma, CNS cells. This study was designed reveal a receptor involved biological activities PEDF. Using yeast two-hybrid screening,...
Gastrin releasing peptide is mitogenic for mouse Swiss 3T3 fibroblasts and certain human small cell lung carcinoma (SCLC) cells but not Balb/c fibroblasts. To identify new molecules associated with the gastrin peptide-responsive phenotype, clones isolated from a differential cDNA library between were used to screen their expression in SCLC lines. Using this approach, we have characterized encoding novel protein. This protein putative transmembrane belonging epidermal growth factor-like...
Preadipocyte differentiation occurs during distinct periods of human development and is a key determinant body mass. Transcriptional events underlying adipogenesis continue to emerge, but the link between chromatin remodeling specific target loci preadipocyte remains elusive. We have identified Krüppel-like factor-6 (KLF6), recently described tumor suppressor gene, as repressor proto-oncogene Delta-like 1 (Dlk1), gene encoding transmembrane protein that inhibits adipocyte differentiation....
Abstract Notch signaling has been extensively implicated in cell-fate determination along the development of immune system. However, a role for fully differentiated cells not clearly defined. We have analyzed expression protein family members during macrophage activation. Resting macrophages express Notch-1, -2, and -4, as well ligands Jagged-1 -2. After treatment with LPS and/or IFN-γ, we observed p38 MAPK-dependent increase Notch-1 mRNA levels. To study activation, forced transient...
We describe the clinical features of 28 patients with juvenile dermatomyositis (JDM) and 1 patient adult-onset (DM), all whom developed lipodystrophy (LD) that could be categorized into 3 phenotypes, generalized, partial, or focal, based on pattern fat loss distribution. LD onset was often delayed, beginning a median 4.6 years after diagnosis DM. Calcinosis, muscle atrophy, joint contractures, facial rash were DM disease found to associated LD. Panniculitis focal lipoatrophy while anti-p155...
Macrophages present different Notch receptors and ligands on their surface. Following macrophage activation by LPS or other TLR ligands, Notch1 expression is upregulated. We report here that signaling increases both basal LPS-induced NF-kappaB activation, favoring the of genes implicated in inflammatory response, such as cytokines TNF-alpha IL-6, enzymes, iNOS. Delta4 seems to be most effective ligand induce increasing transcriptional activity macrophages. show promotes translocation nucleus...
Mouse resistin, a cysteine-rich protein primarily secreted from mature adipocytes, is involved in insulin resistance and type 2 diabetes. Human however, mainly by immune mononuclear cells, it competes with lipopolysaccharide for the binding to Toll-like receptor 4, which could mediate some of well-known proinflammatory effects resistin humans. In addition, has been regulation many cell differentiation proliferation processes, suggesting that different receptors be mediating its numerous...
Notch, a transmembrane receptor member of the homeotic epidermal growth factor-like family proteins, participates in cell-to-cell signaling to control cell fate during development. Activated Notch-1 constructs lacking extracellular region prevent differentiation several mammalian cells vitro. This effect, however, bypasses normal mechanisms interactions which participates. We investigated role hormone-induced adipocyte 3T3-L1 fibroblasts, paradigmatic model adipogenesis that requires...
Translocation-associated Notch homologue (TAN-1), a gene originally cloned from the translocation breakpoint of human T cell leukemia carrying 9:7(q34.3) translocation, encodes protein belonging to Notch/Lin-12/Glp-1 receptor family. These receptors mediate specification numerous fates during development in invertebrates and vertebrates. The intracellular portion Notch/TAN-1 contains six ankyrin repeats that are similar those found cytoplasmic I kappa B proteins. proteins specific inhibitors...
Macrophages activated through Toll receptor triggering increase the expression of A(2A) and A(2B) adenosine receptors. In this study, we show that activation enhances LPS-induced pfkfb3 expression, resulting in an key glycolytic allosteric regulator fructose 2,6-bisphosphate flux. Using shRNA differential receptors, demonstrate mediates, part, induction by LPS, whereas receptor, with lower affinity, cooperates when high levels are present. promoter sequence deletion analysis, site-directed...
Myocardial fibrosis is associated with profound changes in ventricular architecture and geometry, resulting diminished cardiac function. There currently no information on the role of delta-like homologue 1 (Dlk1) regulation fibrotic response. Here, we investigated whether Dlk1 involved fibroblast-to-myofibroblast differentiation regulates myocardial explored molecular mechanism underpinning its effects this process. Using Dlk1-knockout mice adenoviral gene delivery, demonstrate that...
Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from "slow" "fast," whose biophysical properties govern the timing, gradation, and amplitude of force. Here we identify noncanonical Notch ligand Delta-like homolog 1 (Dlk1) as a determinant motor neuron functional diversification. Dlk1, expressed by ~30% is necessary sufficient promote fast signature in mouse chick. Dlk1 suppresses signaling activates expression K(+) channel subunit Kcng4...
dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression known to modulate differentiation signals mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain human marrow (hMSC) an undifferentiated state. To identify molecular mechanisms underlying these effects, we compared basal gene pattern Dlk1-overexpressing hMSC (hMSC-dlk1) versus control (negative for...
The Dlk1 (delta-like-1) gene is a member of the epidermal growth factor (EGF)-like homeotic family. It influences cell–cell interactions between stromal cells and pro-B in vitro. To define vivo role dlk protein B cell development, we established Dlk1−/− mouse model. In spleens mice, transitional numbers were increased ratio subsets was altered. Numbers follicular decreased, while number marginal zone size increased. Loss resulted immunoglobulin G1 (IgG1) IgG3 preimmune sera. Furthermore,...
The epidermal growth factor-like protein Delta-like 1 (DLK1) regulates multiple differentiation processes. It resembles NOTCH ligands structurally and is considered a non-canonical ligand. Given the crucial role of pathway in angiogenesis, we hypothesized that DLK1 could regulate angiogenesis by interfering with NOTCH. We therefore investigated expression function vascular endothelium its regulation angiogenesis. report different species, including human, cow, pig, mouse. Angiogenesis was...
Abstract Delta-like 1/fetal antigen 1 (DLK1/FA-1) is a transmembrane protein belonging to the Notch/Delta family that acts as membrane-associated or soluble regulate regeneration of number adult tissues. Here we examined role DLK1/FA-1 in bone biology using osteoblast-specific Dlk1-overexpressing mice (Col1-Dlk1). Col1-Dlk1 displayed growth retardation and significantly reduced total body weight mineral density (BMD). Micro–computed tomographis (µCT) scanning revealed trabecular cortical...
Adipocyte renewal from preadipocytes has been shown to occur throughout life and contribute obesity, yet very little is known about the molecular circuits that control preadipocyte expansion. The soluble form of factor (also as pref-1) delta-like 1 homolog (DLK1(S)) inhibit adipogenic differentiation; however, impact DLK1 isoforms on proliferation remains be determined. We generated with different levels examined differentially affected gene pathways, which were functionally tested in vitro...
Muscle development and regeneration is tightly orchestrated by a specific set of myogenic transcription factors. However, factors that regulate these essential inducers remain poorly described. Here, we show delta-like 1 homolog (Dlk1), an imprinted gene best known for its ability to inhibit adipogenesis, crucial regulator the program in skeletal muscle. Dlk1(-/-) mice were developmentally retarded their muscle mass function owing inhibition during embryogenesis. Surprisingly however, Dlk1...