A5077394171- Endoplasmic Reticulum Stress and Disease
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- RNA regulation and disease
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Pancreatic function and diabetes
- Toxin Mechanisms and Immunotoxins
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Influenza Virus Research Studies
- CRISPR and Genetic Engineering
- Heat shock proteins research
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Adipose Tissue and Metabolism
- Fungal and yeast genetics research
- Clostridium difficile and Clostridium perfringens research
- Autism Spectrum Disorder Research
- Veterinary medicine and infectious diseases
- Ethics in Clinical Research
- Exercise and Physiological Responses
Vall d'Hebron Hospital Universitari
2019
Centre for Genomic Regulation
2010
New York University
2000-2004
Kyoto University
2004
University of Washington
2002
Centro de Biología Molecular Severo Ochoa
1994-2000
Universidad Autónoma de Madrid
1994-2000
Research Institute of Molecular Pathology
1997
Universidade de Santiago de Compostela
1997
Centro Nacional de Biotecnología
1997
Unfolded and malfolded client proteins impose a stress on the endoplasmic reticulum (ER), which contributes to cell death in pathophysiological conditions. The transcription factor C/EBP homologous protein (CHOP) is activated by ER stress, CHOP deletion protects against its lethal consequences. We find that directly activates GADD34, promotes biosynthesis dephosphorylating phospho-Ser 51 of alpha-subunit translation initiation 2 (eIF2alpha) stressed cells. Thus, impaired GADD34 expression...
Phosphorylation of the α subunit eukaryotic translation initiation factor 2 (eIF2α) on serine 51 integrates general repression with activation stress-inducible genes such as ATF4, CHOP, and BiP in unfolded protein response. We sought to identify new active this phospho-eIF2α–dependent signaling pathway by screening a library recombinant retroviruses for clones that inhibit expression CHOP::GFP reporter. A retrovirus encoding COOH terminus growth arrest DNA damage gene (GADD)34, also known...
The epithelial cells of the gastrointestinal tract are exposed to toxins and infectious agents that can adversely affect protein folding in endoplasmic reticulum (ER) cause ER stress. IRE1 genes implicated sensing responding stress signals. We found express IRE1β, a specific isoform IRE1. BiP protein, marker stress, was elevated colonic mucosa IRE1β–/– mice, and, when dextran sodium sulfate (DSS) induce inflammatory bowel disease, mutant mice developed colitis 3–5 days earlier than did...
P58 IPK is an Hsp40 family member known to inhibit the interferon (IFN)-induced, double-stranded RNA-activated, eukaryotic initiation factor 2α (eIF2α) protein kinase R (PKR) by binding its domain. We find that stress of unfolded proteins in endoplasmic reticulum (ER) activates gene transcription through ER stress-response element promoter region. interacts with and inhibits PKR-like ER-localized eIF2α PERK, which normally activated during ER-stress response protect cells from attenuating...
Phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) on serine 51 is effected by specific stress-activated protein kinases. eIF2α phosphorylation inhibits promoting a cytoprotective gene expression program known as the integrated stress response (ISR). Stress-induced activation GADD34 feeds back negatively this pathway dephosphorylation, however, mutant cells retain significant eIF2α-directed phosphatase activity. We used somatic cell genetic approach to identify encoding...
Influenza virus NS1 protein is an RNA-binding whose expression alters several posttranscriptional regulatory processes, like polyadenylation, splicing, and nucleocytoplasmic transport of cellular mRNAs. In addition, enhances the translational rate viral, but not cellular, To characterize this effect, we looked for targets influenza among translation factors. We found that coimmunoprecipitates with eukaryotic initiation factor 4GI (eIF4GI), large subunit cap-binding complex eIF4F, either in...
The 2A proteinases (2Apro) of certain picornaviruses induce the cleavage eIF4G subunit cap-binding protein complex, eIF4F. Several reports have demonstrated that 2Apro rhinovirus and coxsackievirus B4 cleave directly. However, it was suggested in poliovirus infection, induces activation a cellular proteinase which turn cleaves eIF4G. Furthermore, is not clear whether cleaved as part eIF4F complex or an individual polypeptide. To address these issues, recombinant purified from Sf9 insect...
Efficient cleavage of both forms eukaryotic initiation factor 4G (eIF4G-1 and eIF4G-2) has been achieved in HeLa cells by incubation with hybrid proteins containing poliovirus 2Apro. Entry these into is promoted adenovirus particles. Substantial levels ongoing translation on preexisting cellular mRNAs still continue for several hours after eIF4G degradation. Treatment control hypertonic medium causes an inhibition that reversed upon restoration to normal medium. Protein synthesis not...
Addition of monensin or nigericin after poliovirus entry into HeLa cells prevents the inhibition host protein synthesis by poliovirus. The infected continue to synthesize cellular proteins at control levels for least 8 h infection in presence ionophore. Cleavage p220 (gamma subunit eukaryotic initiation factor 4 [eIF-4 gamma]), a component translation eIF-4F, occurs same extent poliovirus-infected whether not they are treated with monensin. Two hours there is no detectable intact p220, but...
Poliovirus protease 2A pro has been efficiently expressed in HeLa and COS cells upon transfection with vector pTM1‐2A infection the recombinant vaccinia virus bearing T7 RNA polymerase. The poliovirus localizes to cytoplasm of transfected cells, both endoplasmic reticulum vesicles scattered cytoplasm. Cleavage p220, a component initiation factor eIF‐4F, selectively occurs from 5 h post‐infection infected virus. This cleavage correlates time profound inhibition observed synthesis proteins. A...
Poliovirus protease 2A(pro) has been obtained in soluble form as a fusion protein with maltose binding (MBP). Addition of MBP-2A(pro) to rabbit reticulocyte cell-free systems gives rise efficient cleavage the initiation factor translation p220 (eIF-4G). Translation capped mRNA encoding influenza virus NP is severely impaired lysates which proteolytically cleaved. This inhibition dependent on concentration added lysate. Thus, increasing concentrations substantially overcomes blockade...
The effects of transient expression poliovirus 2A pro on p220 cleavage in COS cells have been analyzed. When was cloned plasmid pTM1 and transiently expressed cells, efficient occurred after infection these with a recombinant vaccinia virus hearing phage T7 RNA polymerase. High numbers were transfected pTM1‐2A, as judged by cleavage, thereby allowing an analysis the gene expression. A 40–50% 2R observed ten hours post almost complete (80–90%) 20–25 virus, Profound inhibition protein...
Cleavage of p220, a component the initiation factor eIF-4F, has been correlated with inhibition host translation during poliovirus infection. To obtain p220 cleavage in absence any other gene products, hybrid proteins containing Pseudomonas aeruginosa exotoxin A and protease 2Apro have constructed. The addition molecules to cultured cells did not lead substantial cleavage. However, simultaneous presence toxin replicationally inactive chicken adenovirus particles results efficient intact...
Two hybrid proteins between Pseudomonas aeruginosa exotoxin A (PE) and poliovirus protease 2Apro have been generated. One protein contains the sequence replacing region of PE corresponding to amino acids 413-607. The other in addition transforming growth factor sequence. two were efficiently synthesized E. coli cells using inducible pET vectors. Both toxins cleaved p220 (eIF-4 gamma) when recombinant plasmids transfected COS infected with vaccinia virus bearing T7 RNA polymerase gene.
Mammalian Ran-binding protein-1 (RanBP1) and its fission yeast homologue, sbp1p, are cytosolic proteins that interact with the GTP-charged form of Ran GTPase through a conserved domain (RBD). In vitro, this interaction can accelerate GTPase-activating protein–mediated hydrolysis GTP on turnover nuclear import export complexes. To analyze RanBP1 function in vivo, we expressed exogenous RanBP1, RBD each mammalian cells, wild-type yeast, whose endogenous sbp1 gene was disrupted. cells...
Influenza virus NS1 protein is an RNA-binding whose expression alters several posttranscriptional regulatory processes, like polyadenylation, splicing, and nucleocytoplasmic transport of cellular mRNAs. In addition, enhances the translational rate viral, but not cellular, To characterize this effect, we looked for targets influenza among translation factors. We found that coimmunoprecipitates with eukaryotic initiation factor 4GI (eIF4GI), large subunit cap-binding complex eIF4F, either in...