A5038051768- RNA Research and Splicing
- RNA modifications and cancer
- Neurogenetic and Muscular Disorders Research
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Neurogenesis and neuroplasticity mechanisms
- Peripheral Neuropathies and Disorders
- DNA Repair Mechanisms
- Hereditary Neurological Disorders
- Nuclear Structure and Function
- RNA regulation and disease
- Amyotrophic Lateral Sclerosis Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Neuroscience and Neuropharmacology Research
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Erythrocyte Function and Pathophysiology
- Genetics and Neurodevelopmental Disorders
- Muscle Physiology and Disorders
- Graphene and Nanomaterials Applications
- Prion Diseases and Protein Misfolding
- Birth, Development, and Health
Universidad de Cantabria
2016-2025
Instituto de Investigación Marqués de Valdecilla
2016-2025
Centro de Investigación Biomédica en Red
2013-2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2015-2024
University of Tübingen
2023
Hospital Universitario Fundación Jiménez Díaz
2020
Marqués de Valdecilla University Hospital
1982-2015
Instituto de Biomedicina y Biotecnología de Cantabria
2004-2010
Consejo Superior de Investigaciones Científicas
2008
Universidad Cardenal Herrera CEU
1991-2005
The β-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1α,25-dehydroxyvitamin D3) analogues are candidate drugs to treat this neoplasia. We show that these compounds promote the differentiation of human carcinoma SW480 cells expressing D receptors (VDRs) (SW480-ADH) but not a malignant subline (SW480-R) or metastasic derivative (SW620) lacking VDR. 1α,25(OH)2D3 induced expression E-cadherin and other adhesion proteins (occludin, Zonula...
The RNA binding protein TDP-43 forms intranuclear or cytoplasmic aggregates in age-related neurodegenerative diseases. In this study, we found that binding-deficient (produced by neurodegeneration-causing mutations posttranslational acetylation its recognition motifs) drove demixing into liquid spherical shells with cores. These droplets, which named "anisosomes", have exhibit birefringence, thus indicating crystal formation. Guided mathematical modeling, identified the primary components of...
Abstract Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading fatal diseases. Senescent cells are main driver fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report cellular senescence, multiple types in mice humans characterized by the accumulation iron. We show vascular hemolytic injuries efficient triggering iron accumulation, which turn cause senescence...
ADAR1 and ADAR2 are editing enzymes that deaminate adenosine to inosine in long double stranded RNA duplexes specific pre-mRNA transcripts. Here, we show full-length N-terminally truncated forms of simultaneously expressed HeLa COS7 cells owing the usage alternative starting methionines. Because N-terminus contains a nuclear export signal, protein localizes predominantly cytoplasm, whereas exclusively accumulate nucleolus. ADAR2, which lacks region homologous N-terminal domain ADAR1, nucleus...
Cajal bodies (CBs) are nuclear suborganelles involved in the biogenesis of small ribonucleoproteins (snRNPs). In addition to snRNPs, they highly enriched basal transcription and cell cycle factors, nucleolar proteins fibrillarin (Fb) Nopp140 (Nopp), survival motor neuron (SMN) protein complex, CB marker protein, p80 coilin. We report generation knockout mice lacking COOH-terminal 487 amino acids Northern Western blot analyses demonstrate that we have successfully removed full-length coilin...
The spliceosomal snRNAs U1, U2, U4, and U5 are synthesized in the nucleus, exported to cytoplasm assemble with Sm proteins, reimported nucleus as ribonucleoprotein particles. Recently, two novel proteins involved biogenesis of small nuclear ribonucleoproteins (snRNPs) were identified, Spinal muscular atrophy disease gene product (SMN) its associated protein SIP1. It was previously reported that HeLa cells, SMN SIP1 form discrete foci located next Cajal (coiled) bodies, so-called “gemini...
Intestine is a major target of vitamin D and several studies indicate an association between deficiency inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk mortality. However, the putative effects 1α,25-dihydroxyvitamin D3 (calcitriol), active metabolite, on human colonic stem cells are unknown. Here we show by immunohistochemistry RNAscope in situ hybridization that receptor (VDR) unexpectedly expressed LGR5+ colon tissue normal tumor organoid cultures...
The escape of mitochondrial double-stranded dsRNA (mt-dsRNA) into the cytosol has been recently linked to a number inflammatory diseases. Here, we report that release mt-dsRNA is general feature senescent cells and critical driver their secretome, known as senescence-associated secretory phenotype (SASP). Inhibition RNA polymerase, sensors RIGI MDA5, or master signaling protein MAVS, all result in reduced expression SASP, while broadly preserving other hallmarks senescence. Moreover, are...
The active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes differentiation of colon cancer cells through the activation receptor (VDR), a transcription factor nuclear superfamily. Additionally, 1,25(OH)2D3 has several nongenomic effects uncertain relevance. We show that induces transcription-independent Ca2+ influx RhoA–Rho-associated coiled kinase (ROCK). This requires VDR is followed by p38 mitogen-activated protein (p38MAPK) mitogen-...
Abstract Glioblastoma (GBM) is associated with infiltration of peritumoral (PT) parenchyma by isolated tumor cells that leads to regrowth. Recently, GBM stem-like or initiating (GICs) have been identified in the PT area, but whether these GICs enhanced migratory and invasive capabilities compared from mass (TM) presently unknown. We infiltrated tissue TM three patients found an advantage over two-dimensional three-dimensional migration invasion assays. Interestingly, display a high...
Nuclear bodies represent a heterogeneous class of nuclear structures. Herein, we describe that subset is highly enriched in components the ubiquitin–proteasome pathway proteolysis. We coined term clastosome (from Greekklastos, broken and soma, body) to refer this type body. Clastosomes contain high concentration 1) ubiquitin conjugates, 2) proteolytically active 20S core 19S regulatory complexes 26S proteasome, 3) protein substrates proteasome. Although detected variety cell types,...
Ras GTPases include the isoforms H-Ras, K-Ras, and N-Ras. Despite their great biochemical biological similarities, evidence is mounting suggesting that proteins may not be functionally redundant. A widespread strategy for studying small utilization of dominant inhibitory mutants specifically block activation respective wild-type proteins. As such, H-Ras N17 has proved to extremely valuable as a tool probe functions. However, comparative study on specificities H-, K-, N-Ras been approached...
Trigeminal ganglion neurons comprise three main cell body-size types. This size heterogeneity provides an excellent neuronal model to study the size-dependent organization and dynamics of nucleoli, Cajal (coiled) bodies (CBs), nuclear speckles pre-mRNA splicing factors, structures that play a key role in normal physiology. We have analyzed number nucleoli CBs structural molecular types by using immunofluorescence with antibodies recognize (fibrillarin), (coilin), (snRNPs), confocal...
The immunosuppressive and antiinflammatory actions of glucocorticoid hormones are mediated by their transrepression activating protein-1 (AP-1) nuclear factor-kappa B (NFκB) transcription factors. Inhibition the c-Jun NH2-terminal kinase (JNK) signaling pathway, main mediator AP-1 activation, has been described in extracts hormone-treated cells. Here, we show confocal laser microscopy, enzymatic assays, immunoblotting that synthetic dexamethasone inhibited tumor necrosis factor α...
Recent findings indicate that in addition to its location the peripheral plasma membrane, H-Ras is found endomembranes like endoplasmic reticulum and Golgi complex. In these locations functional can efficiently engage downstream effectors, but little known about how activation regulated environments. Here we show RasGRF family exchange factors, both endogenous ectopically expressed, are present not With aid of constructs specifically tethered reticulum, complex, demonstrate RasGRF1 RasGRF2...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and muscle atrophy related to the loss of upper lower motor neurons (MNs) without curative treatment. There experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt) retinoid-X receptor agonist used treatment cutaneous lymphoma with favourable safety profile whose effects have been recently investigated other diseases. In this study, we analyze...