A5058524912- Cell death mechanisms and regulation
- Chronic Lymphocytic Leukemia Research
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- Heat shock proteins research
- Acute Lymphoblastic Leukemia research
- Ubiquitin and proteasome pathways
- Immune Response and Inflammation
- Liver physiology and pathology
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Mitochondrial Function and Pathology
- Cancer Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Genetics, Aging, and Longevity in Model Organisms
Universidad Autónoma de Madrid
2013-2024
Consejo Superior de Investigaciones Científicas
1991-2024
Instituto de Investigaciones Biomédicas Sols-Morreale
2014-2024
Hospital La Paz Institute for Health Research
2015-2024
Hospital Universitario La Paz
2015-2021
Institute of Human Virology
2018
Temuco Catholic University
2010
Centro de Biología Molecular Severo Ochoa
1994-2008
Sanford Burnham Prebys Medical Discovery Institute
1999-2008
Institute for Medical Research
2005-2008
We have identified three new tumor necrosis factor-receptor associated factor (TRAF) domain-containing proteins in humans using bioinformatics approaches, including: MUL, the product of causative gene Mulibrey Nanism syndrome; USP7 (HAUSP), an ubiquitin protease; and SPOP, a POZ protein. Unlike classical TRAF family involved TNF receptor (TNFR) signaling, domains (TDs) USP7, SPOP are located near NH2 termini or central region these proteins, rather than carboxyl end. MUL capable bindingin...
Ischemia-reperfusion (IR) injury induces endoplasmic reticulum (ER) stress and cell death. Bax Inhibitor-1 (BI-1) is an evolutionarily conserved ER protein that suppresses death abundantly expressed in both liver kidney. We explored the role of BI-1 protection from IR by using bi - 1 knockout mice, employing models transient hepatic or renal artery occlusion. Compared to wild-type bi-1 mice subjected exhibited these characteristics: ( i ) increased histological injury; ii serum...
The costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with FcγR interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8N/CEGa1, consisting three single-chain variable fragments and anti-EGFR single-domain positioned extended hexagonal conformation around the...
Modulating signal transduction pathways represents a promising approach for altering the biological behaviour of haemopoietic malignancies. B‐cell chronic lymphocytic leukaemia (B‐CLL) cells were treated in vitro with CD40‐ligand (CD40L) (CD154) or protein kinase C modulator Bryostatin‐1, exploring effects on: (a) sensitivity to apoptosis induction by chemotherapeutic drugs (fludarabine, dexamethasone) anti‐Fas antibody; (b) expression apoptosis‐regulatory proteins (Bcl‐2, Bcl‐X, Mcl‐1, Bax,...
The common neurotrophin receptor, p75NTR, has been shown to signal in the absence of Trk tyrosine kinase receptors, including induction neural apoptosis and activation NF-κB. However, mechanisms by which p75NTR initiates these intracellular transduction pathways are unknown. Here we report interactions between six members TRAF (tumor necrosis factor receptor-associated factors) family proteins. binding different proteins was mapped distinct regions p75NTR. Furthermore, TRAF4 interacted with...
Inhibitor of apoptosis proteins (IAPs) regulate primarily by inhibiting caspase-family proteases. However, many IAPs also possess E3 ligase (ubiquitin-protein isopeptide ligase) activities implicated in both caspase-dependent and -independent functions these proteins. Here, we compared the structural features cIAP1 responsible for its interactions with two known target proteins, TRAF2 SMAC. The N-terminal (BIR1) C-terminal (BIR3) BIR domains were determined to be necessary sufficient binding...
Abstract TNFR-associated factors (TRAFs) constitute a family of adapter proteins that associate with particular TNF receptors. Humans and mice contain six TRAF genes, but little is known about their in vivo expression at the single cell level. The locations TRAF1, TRAF2, TRAF5, TRAF6 were determined human mouse tissues by immunohistochemistry. Striking diversity was observed patterns immunostaining obtained for each protein, suggesting independently regulated type-specific manner. Dynamic...
Abstract Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL or Apo2L) has been shown to induce apoptosis specifically in cancer cells while sparing normal tissues. Unfortunately not all respond TRAIL; therefore, TRAIL sensitizing agents are currently being explored. We have identified synthetic triterpenoids, including 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivative 1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole (CDDO-Im), which sensitize...
Ubc13 is a ubiquitin-conjugating enzyme responsible for noncanonical ubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in Toll-like receptor and TNF-family cytokine signaling, which are regulators innate immunity. Gene ablation was used to study the function mice. Whereas homozygous ubc13 gene disruption resulted embryonic lethality, heterozygous ubc13(+/-) mice appeared normal, without alterations immune cell populations. Haploinsufficient were...
Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking mechanisms with inflammatory responses through NFκB induction. Proteins involved induction commonly contain evolutionarily conserved domains that can serve signatures identification by bioinformatics methods. Using combination public (NCBI)...
Abstract We explored the location and function of human cIAP1 protein, a member inhibitor apoptosis protein (IAP) family. Unlike family X-linked IAP (XIAP), which was predominantly cytoplasmic, localized almost exclusively to nuclei in cells, as determined by immunofluorescence microscopy subcellular fractionation methods. Interestingly, apoptotic stimuli induced nuclear export cIAP1, blocked chemical caspase inhibitor. In dividing released into cytosol early mitosis, then reaccumulated late...