A5047605136- Autophagy in Disease and Therapy
- Signaling Pathways in Disease
- Extracellular vesicles in disease
- Immune Cell Function and Interaction
- Barrier Structure and Function Studies
- T-cell and B-cell Immunology
- Neuroinflammation and Neurodegeneration Mechanisms
- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Calcium signaling and nucleotide metabolism
- Immune cells in cancer
- Calpain Protease Function and Regulation
- PARP inhibition in cancer therapy
- Toxoplasma gondii Research Studies
- RNA Interference and Gene Delivery
- Aldose Reductase and Taurine
- Cannabis and Cannabinoid Research
- Endoplasmic Reticulum Stress and Disease
- Protein Degradation and Inhibitors
- Biocrusts and Microbial Ecology
- Cancer Cells and Metastasis
- Aquatic Ecosystems and Phytoplankton Dynamics
- Immunodeficiency and Autoimmune Disorders
- Ferroptosis and cancer prognosis
- Trypanosoma species research and implications
Universidad de Murcia
2006-2024
Instituto Murciano de Investigación Biosanitaria
2016-2024
Albert Einstein College of Medicine
2010-2017
Hospital Universitario Virgen de la Arrixaca
2004-2010
National Institute of Pathology
2010
Abstract Macroautophagy is a highly conserved mechanism of lysosomal-mediated protein degradation that plays key role in maintaining cellular homeostasis by recycling amino acids, reducing the amount damaged proteins, and regulating levels response to extracellular signals. We have found macroautophagy induced after effector T cell activation. Engagement TCR CD28 results enhanced microtubule-associated 1 light chain 3 (LC3) processing, increased numbers LC3-containing vesicles, LC3 flux,...
Significance Glioblastoma (GB) is the most lethal brain malignancy without an effective treatment. In this study, we demonstrate that tumor-induced change in chaperone-mediated autophagy (CMA) host perivascular cells a targetable process to prevent GB progression. CMA regulates pericyte interaction with tumor and sustains acquired immunosuppressive function of pericytes, which required for survival. Blockage results changes protein levels involved cell-to-cell affects secretory phenotype,...
Chaperone-mediated autophagy (CMA) is a selective proteolytic pathway in the lysosomes. Proteins are recognized one by through detection of KFERQ motif or, at least, KFERQ-like motif, heat shock cognate protein 70 (Hsc70), molecular chaperone. CMA substrates and delivered to lysosomal receptor, lysosome-associated membrane 2A (LAMP-2A), only limiting component this pathway, transported lumen with help another resident chaperone HSp90. Since approximately 75% proteins reported have canonical,...
A hallmark of aging is an imbalance between production and clearance reactive oxygen species increased levels oxidatively damaged biomolecules. Herein, we demonstrate that splenic nodal antigen-presenting cells purified from mice accumulate modified proteins with side-chain carbonylation, advanced glycation end products, lipid peroxidation. Furthermore, show the endosomal accumulation interferes efficient processing exogenous antigens degradation macroautophagy-delivered proteins. In support...
The establishment of immune tolerance during Glioblastoma Multiforme (GBM) progression, is characterized by high levels expression anti-inflammatory cytokines, which suppress the function tumor assocciated myeloid cells, and activation expansion antigen specific T cells. However, mechanisms underlying failed anti-tumor response around blood vessels GBM, are poorly understood. consequences possible interactions between cancer cells perivascular compartment might affect growth. In this work we...
Abstract Background Accumulating evidence suggests an important role for the enzyme poly(ADP-ribose) polymerase-1 (PARP-1) as integral part of gene expression regulatory machinery during development and in response to specific cellular signals. PARP-1 might modulate through its catalytic activity leading poly(ADP-ribosyl)ation nuclear proteins or by physical association with relevant proteins. Recently, we have shown that is activated T cell activation. However, proposed reprogramming upon...
Background: The lack of knowledge the progression mechanisms glioblastoma (GB), most aggressive brain tumor, contributes to absence successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. possible impact that GB-induced CMA PC on other functions might be useful future prognosis/treatment, not...
ABSTRACT The adaptor protein LAT has a prominent role in the transduction of intracellular signals elicited by TCR/CD3 complex. Upon TCR engagement, becomes tyrosine-phosphorylated and thereby, recruits to membrane several proteins implicated activation downstream signaling pathways. However, little is known about other conserved motifs present sequence. Here, we report that contains serine-based motifs, which are essential for proper signal through TCR. Mutation these serine human T cell...
In response to suboptimal activation, T cells become hyporesponsive, with a severely reduced capacity proliferate and produce cytokines upon reencounter antigen. Chromatin analysis of made tolerant by use different in vitro vivo approaches reveals that the expression gamma interferon (IFN-γ) is epigenetically silenced anergic effector TH1 cells. those cells, calcium signaling triggers Tle4, member Groucho family corepressors, which then recruited distal regulatory element Ifng locus causes...
Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers due to its complex tumor microenvironment (TME). We previously showed that GB progression dependent on aberrant induction chaperone-mediated autophagy (CMA) in pericytes (PCs), which promotes TME immunosuppression through PC secretome. The secretion extracellular matrix (ECM) proteins with anti-tumor (Lumican) pro-tumoral (Osteopontin, OPN) properties was shown be regulation GB-induced CMA PCs. As biomarkers are...
Intratumoral pericytes (PC) do not share the same tumor niche as peritumoral PC. Furthermore, glioblastoma multiforme (GB) cells seem to affect them equally. Therefore, for a better understanding of effects GB on PC, in this chapter, we will classify according whether they are intratumoral or focusing mainly effects, which have future prospects finding effective therapies cancer. Recently, it has been shown that PC could be main target infiltration front and fundamental role proliferation,...