A5034086697- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- interferon and immune responses
- RNA Research and Splicing
- RNA modifications and cancer
- Bacterial Identification and Susceptibility Testing
- Immune cells in cancer
- Mitochondrial Function and Pathology
- Asthma and respiratory diseases
- Sphingolipid Metabolism and Signaling
- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Legionella and Acanthamoeba research
- ATP Synthase and ATPases Research
- CRISPR and Genetic Engineering
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Mast cells and histamine
- Water Treatment and Disinfection
Instituto de Biomedicina y Genética Molecular de Valladolid
2017-2025
Universidad de Valladolid
2015-2025
Consejo Superior de Investigaciones Científicas
2002-2025
Departamento de Salud
2015-2016
Brigham and Women's Hospital
2004-2015
Hospital Clínico Universitario de Valladolid
2011-2012
Harvard University
2001-2008
Beth Israel Deaconess Medical Center
2001-2006
Beth Israel Deaconess Hospital
2006
Harvard University Press
2001-2003
Rapid IgE desensitization provides temporary tolerization for patients who have presented severe hypersensitivity reactions to food and drugs, protecting them from anaphylaxis, but the underlying mechanisms are still incompletely understood. Thus, here we develop an effective reproducible in vitro model of rapid mouse BM-derived mast cells (BMMCs) under physiologic calcium conditions, characterize its antigen specificity primary events. BMMCs were challenged with DNP-human serum albumin...
The mitochondrial genome relies heavily on post-transcriptional events for its proper expression, and misregulation of this process can cause genetic diseases in humans. Here, we report that a novel translational variant Fas-activated serine/threonine kinase (FASTK) co-localizes with RNA granules is required the biogenesis ND6 mRNA, mitochondrial-encoded subunit NADH dehydrogenase complex (complex I). We show ablating FASTK expression cultured cells mice results specifically loss mRNA...
The functions of macrophages are tightly regulated by their metabolic state. However, the role mitochondrial electron transport chain (ETC) in macrophage remains understudied. Here, we provide evidence that succinate dehydrogenase (SDH)/complex II (CII) is required for respiration and plays a controlling effector responses macrophages. We find absence catalytic subunits Sdha Sdhb impairs ability to effectively stabilize HIF-1α produce pro-inflammatory cytokine IL-1β response LPS stimulation....
This study aimed to identify novel isoforms of mouse succinate dehydrogenase complex flavoprotein subunit A (Sdha) arising from internal exon skipping, analogous the process observed in human ortholog SDHA. We identified a isoform, designated Δ3-10, which lacked final 104 nucleotides 3 and all exons 4 through 10, yet did not alter reading frame. The Δ3-10 Sdha cDNA was cloned into expression vectors, overexpression resulted protein localized mitochondria. However, endogenous detected with...
X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency characterized by extreme susceptibility to Epstein-Barr virus. The XLP gene product <i>SH2D1A</i> (SAP) interacts via its SH2 domain with motif (TIY<i>XX</i>V) present in the cytoplasmic tail of cell-surface receptors CD150/SLAM, CD84, CD229/Ly-9, and CD244/2B4. Characteristically, SH2D1A three-pronged interaction Tyr<sup>281</sup> CD150 can occur absence phosphorylation. Here we analyze effect protein missense...
Gene array analysis revealed that a subset of mRNAs overexpressed in macrophages lacking the destabilizing factor TTP are also translational silencer TIA-1. We confirmed representative transcript, apobec-1, is significantly stabilized cells Tethering TIA-1 to reporter transcript promotes mRNA decay, suggesting TIA-1-mediated silencing can render susceptible decay machinery. inhibited by small interfering RNAs targeting components either 5′-3′ (e.g. DCP2) or 3′-5′ exosome component Rrp46)...
The CD5 lymphocyte surface glycoprotein is a coreceptor involved in the modulation of antigen-specific receptor-mediated activation and differentiation signals. Although first considered costimulatory molecule mature peripheral T cells, recent studies CD5-/- mice have opened possibility that may also mediate inhibitory signals attenuate TCR/CD3- BCR-mediated triggering thymocytes subgroup B cells (B-1a cells), respectively. ultimate molecular basis for these differential modulatory...
The free Src homology 2 (SH2) domain protein SAP, encoded by the X‐linked lymphoproliferative disease gene SH2D1A, controls signal transduction initiated engagement of SLAM‐related receptors in T and NK cells. Here we demonstrate that SAP is required for phosphorylation both SLAM Ly9 thymocytes peripheral Furthermore, vitro interaction studies yeast two‐hybrid analyses indicated binds directly to FynT Lck. While bound SH3 kinase FynT, solely existence a strong between prompted us study role...
The Fas-activated serine/threonine kinase (FASTK) family of proteins has recently emerged as a central regulator mitochondrial gene expression through the function an unusual RNA-binding domain named RAP (for abundant in Apicomplexans), shared by all six members family. Here we describe role one less characterized members, FASTKD3, RNA metabolism. First, show that, contrast to FASTK, FASTKD2, and FASTKD5, FASTKD3 does not localize granules, which are sites processing maturation mtRNAs...
The Fas-activated serine/threonine phosphoprotein (FAST) is tethered to the outer mitochondrial membrane, where it interacts with BCL-X(L) (17). Here we show that RNA interference-mediated knockdown of endogenous FAST results in apoptosis, whereas overexpressed recombinant inhibits Fas- and UV-induced indicating a survival protein. antiapoptotic effects are regulated by interactions translational silencer TIA-1: mutant lacking its TIA-1-binding domain does not inhibit TIA-1 FAST. Because...
Abstract CD5 is a lymphocyte surface glycoprotein with long cytoplasmic domain suitable for phosphorylation and signal transduction, which involved in the modulation of Ag-specific receptor-mediated activation differentiation signals. In this study, we use Jurkat T cell transfectants tail mutants to reveal sites relevant transduction. Our results show that casein kinase II (CKII) responsible constitutive molecules at cluster three serine residues located extreme C terminus (S458, S459,...
Fas-activated serine/threonine phosphoprotein (FAST) is a survival protein that tethered to the outer mitochondrial membrane. In cells subjected environmental stress, FAST moves stress granules, where it interacts with TIA1 modulate process of stress-induced translational silencing. Both and are also found in nucleus, promotes inclusion exons flanked by weak splice recognition sites such as exon IIIb fibroblast growth factor receptor 2 (FGFR2) mRNA. Two-hybrid interaction screens biochemical...
Abstract Background Inherited retinal dystrophies (IRD) are one of the main causes incurable blindness worldwide. IRD caused by mutations in genes that encode essential proteins for retina, leading to photoreceptor degeneration and loss visual function. generates an enormous global financial burden due lack understanding a significant part its pathophysiology, molecular diagnosis, near absence non-palliative treatment options. Patient-derived induced pluripotent stem cells (iPSC) seem be...
Abstract The CD5 lymphocyte surface glycoprotein is a coreceptor involved in the modulation of Ag-specific receptor-mediated activation and differentiation signals. molecular basis for its modulatory properties not yet well understood. In present study we describe early biochemical events triggered by stimulation, which include phosphatidylcholine-specific phospholipase C (PC-PLC)-dependent acidic sphingomyelinase (A-SMase) normal lymphoblastoid T B cells. functional coupling PC-PLC A-SMase...