A5025418838- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Cellular transport and secretion
- Nuclear Structure and Function
- Chronic Obstructive Pulmonary Disease (COPD) Research
- RNA modifications and cancer
- Plant nutrient uptake and metabolism
- Nutrition and Health in Aging
- Genomics and Chromatin Dynamics
- Skin and Cellular Biology Research
- Cardiomyopathy and Myosin Studies
- Pulmonary Hypertension Research and Treatments
- Photosynthetic Processes and Mechanisms
- Glycosylation and Glycoproteins Research
- Retinal Development and Disorders
- Fungal and yeast genetics research
- RNA Interference and Gene Delivery
- Enzyme Structure and Function
- 14-3-3 protein interactions
- Dermatological and COVID-19 studies
- Monoclonal and Polyclonal Antibodies Research
- Muscle metabolism and nutrition
- Eosinophilic Disorders and Syndromes
- Ubiquitin and proteasome pathways
- Pancreatic function and diabetes
Oxford Nanoimaging (United Kingdom)
2023-2024
Hospital Pedro Hispano
2022
University of Oxford
2012-2020
Ecological Society of America
2018
John Wiley & Sons (United States)
2018
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2009-2018
Universitat de Barcelona
1990-2018
IFC Research (United Kingdom)
2018
Espregueira Mendes Clinic
2018
Wellcome Centre for Cell Biology
2017
PP2A-B55 is one of the major phosphatases regulating cell division. Despite its importance for temporal control during mitotic exit, how B55 substrates are recognized and differentially dephosphorylated unclear. Using phosphoproteomics combined with kinetic modeling to extract B55-dependent rate constants, we have systematically identified assigned their order in exit. These share a bipartite polybasic recognition determinant (BPR) flanking Cdk1 phosphorylation site. Experiments show that...
We have used antibodies directed against a number of nuclear pore complex (NPC) proteins to determine their mutual interactions and location within the three-dimensional structure NPC. A monoclonal antibody, termed QE5, recognized three NPC polypeptides, p250, NUP153, p62 on Western blots, labeled envelope several cultured cell lines by immunofluorescence microscopy. These polypeptides contained O-linked N-acetylglucosamine residues were released from detergent/high-salt treatment as...
ABSTRACT Nuclear pore complexes (NPCs) are extremely elaborate structures that mediate the bidirectional movement of macromolecules between nucleus and cytoplasm. With a mass about 125 MDa, NPCs thought to be composed 50 or more distinct protein subunits, each present in multiple copies. During mitosis higher cells nuclear envelope is disassembled its components, including NPC dispersed throughout mitotic At end mitosis, all these components reutilized. Using both conventional digital...
Chronic obstructive pulmonary disease (COPD) is associated with structural and functional changes in the circulation that commence at an early stage. To investigate whether vascular endothelial growth factor (VEGF) might be implicated as a mediator COPD-associated changes, we studied surgical specimens obtained from 19 nonsmokers, 21 smokers normal lung function, 28 patients moderate COPD, 10 severe emphysema. The expression of VEGF muscular arteries was evaluated by immunohistochemistry,...
Nup153 is a large (153 kD) O-linked glyco-protein which component of the basket structure located on nucleoplasmic face nuclear pore complexes. This protein exhibits tripartite consisting zinc finger domain flanked by (60-70 NH2- and COOH-terminal domains. When full-length human expressed in BHK cells, it accumulates appropriately at envelope. Targeting information for resides NH2-terminal since this region molecule can direct an ordinarily cytoplasmic protein, pyruvate kinase, to complex....
Many protein kinases are activated by a conserved regulatory step involving T-loop phosphorylation. Although there is considerable focus on kinase activator proteins, the importance of specific phosphatases reversing activation has been underappreciated. We find that phosphatase 6 (PP6) holoenzyme major for Aurora A, an essential mitotic kinase. Loss PP6 function depletion catalytic or subunits interferes with spindle formation and chromosome alignment because increased A activity....
Cytokinesis follows separase activation and chromosome segregation. This order is ensured in budding yeast by the mitotic exit network (MEN), where Cdc14p dephosphorylates key conserved Cdk1-substrates exemplified anaphase spindle-elongation protein Ase1p. However, metazoans, MEN Cdc14 function not conserved. Instead, PP2A-B55α/ENSA/Greatwall (BEG) pathway controls human Ase1p ortholog PRC1. In this pathway, PP2A-B55 inhibition coupled to Cdk1-cyclin B activity, whereas maintained cyclin...
Cytokinesis requires a membrane-remodeling and fission event termed abscission that occurs after chromosome segregation, cleavage furrow formation, contraction have completed. In this study, we show how factor recruitment is controlled by the Polo-like kinase 1 (Plk1). At metaphase-anaphase transition, Plk1 initiates formation then progressively degraded during mitotic exit. During period, phosphorylates Cep55 in trans prevents its untimely to anaphase spindle. A phosphorylation site mutant...
The ancestral Rab GTPase Rab18 and both subunits of the Rab3GAP complex are mutated in human neurological developmental disorder Warburg Micro syndrome. Here, we demonstrate that is a specific guanine nucleotide exchange factor (GEF). localizes to endoplasmic reticulum (ER) necessary for ER targeting Rab18. It also sufficient promote membrane recruitment Disease-associated point mutations conserved residues either Rab3GAP1 (T18P E24V) or Rab3GAP2 (R426C) result loss GEF membrane-targeting...
The spindle assembly checkpoint (SAC) monitors correct attachment of chromosomes to microtubules, an important safeguard mechanism ensuring faithful chromosome segregation in eukaryotic cells. How the SAC signal is turned off once all have successfully attached remains unresolved question. Mps1 phosphorylation Knl1 results recruitment proteins Bub1, Bub3, and BubR1 kinetochore production wait-anaphase signal. silencing therefore expected involve a phosphatase opposing Mps1. Here we...
Anaphase central spindle formation is controlled by the microtubule-stabilizing factor PRC1 and kinesin KIF4A. We show that an MKlp2-dependent pool of Aurora B at spindle, rather than global activity, regulates KIF4A accumulation spindle. phosphorylation stimulates maximal microtubule-dependent ATPase activity promotes its interaction with PRC1. In presence phosphorylated KIF4A, microtubules grew more slowly showed long pauses in growth, resulting generation shorter PRC1-stabilized...
SummaryRab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, Rab14 candidate Rab GDP-GTP exchange factors (GEFs) FAM116A AVL9 are required for its GEF localize to act on an intermediate compartment of transferrin-recycling pathway prior Rab11 after Rab5 Rab4. This recycling has specific functions in migrating cells discrete from early endosomes. Rab14-depleted show increased N-cadherin levels at junctional complexes...
One of the major hurdles that has hindered success chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing same epitopes on normal tissues. To elevate safety profile CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling activation only in presence a highly expressed tumor associated (TAA) but not when recognizing at physiological level healthy cells. Using direct stochastic optical reconstruction microscopy...
Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and respiration seven low mass index (BMI L ), eight normal N ) healthy controls. All them underwent a vastus lateralis biopsy which structure, vitro respiratory function, uncoupling protein 3 (UCP3) mRNA...
In mitosis, animal cells lose their adhesion to the surrounding surfaces and become rounded. During mitotic exit, they reestablish these adhesions at same time physically contract divide. How competing processes are spatially segregated cell cortex remains mysterious. To address this question, we define specific effector pathways used by RhoA Rac1 in cells. We demonstrate that MKlp1–CYK4 centralspindlin complex is a guanosine triphosphatase–activating protein (GAP) for not CYK4 negatively...
Chronic Obstructive Pulmonary Disease (COPD) has significant systemic effects beyond the lungs amongst which muscle wasting is a prominent contributor to exercise limitation and an independent predictor of morbidity mortality. The molecular mechanisms leading skeletal dysfunction/wasting are not fully understood likely be multi-factorial. need develop therapeutic strategies aimed at improving requires better understanding responsible for these abnormalities. Microarrays powerful tools that...
The mitotic kinase Aurora B is concentrated at the anaphase central spindle by kinesin MKlp2 during exit and cytokinesis. This pool of phosphorylates substrates including KIF4A to regulate length. In this paper, we identify a counteracting system in which PP2A–B56γ -ε, but not PP2A–B56α, -β, -δ, are maintained KIF4A. Biochemical assays show that can dephosphorylate T799 site on thereby counteract B– microtubule-stimulated ATPase activity agreement with these observations, combined silencing...
Mutations in the PPP6C catalytic subunit of protein phosphatase 6 (PP6) are drivers for development melanoma. Here we analyse a panel melanoma-associated mutations and find that these generally compromise assembly PP6 holoenzyme activity towards model substrate. Detailed analysis one mutant, PPP6C-H114Y, both primary melanoma engineered cell lines reveals it is destabilized undergoes increased turnover by proteasome. Global substrates mass spectrometry identifies oncogenic kinase Aurora-A as...
Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange GTP hydrolysis mechanisms. Despite conservation of active-site residues, the Ras-related Rab pathway differs from between different Rabs. Analysis DENND1-Rab35, Rabex-Rab5, TRAPP-Rab1 DrrA-Rab1 suggests Rabs have potential for distinct GDP-release pathways. Conserved residues in switch II region stabilising nucleotide-free form differentiate these For DENND1-Rab35 glutamine, often mutated to create...
The short filaments extending from the cytoplasmic face of nuclear pore complexes are thought to contain docking sites for import substrates. One component these is large O-linked glycoprotein CAN/Nup214. Immunoprecipitation studies carried out under nondenaturing conditions, and using a variety antibodies, reveal novel nonglycosylated nucleoporin, Nup84, that tightly associated with Consistent such an association, Nup84 found be exposed on complex. cDNA sequence analyses indicate contains...
alpha-Spectrin, myosin light chain kinase (MLCK), and caldesmon have been detected in the nuclei of rat liver cells by 125I-calmodulin overlay, immunoblotting, immunocytochemical methods. alpha-Spectrin is localized nuclear matrix, envelope, pores. It has also inside form small aggregates. MLCK present nucleoli, a nuclease extract (S1 subfraction) but not Caldesmon shows diffuse distribution pattern it nucleoli. Since all these proteins are components actin-myosin motility systems presence...
Journal Article Molecular structure of the gene and 5′-flanking region human lymphocyte immunoglobulin E receptor Get access Ueli Suter, Suter Department Biotechnology, Ciba-Gcigy Ltd4002 Basel, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Ricardo Bastos, Bastos Hans Hofstetter * To whom correspondence should be addressed Nucleic Acids Research, Volume 15, Issue 18, 25 September 1987, Pages 7295–7308, https://doi.org/10.1093/nar/15.18.7295...
Mitogen-activated protein kinase 8 interacting 3 (MAPK8IP3/JIP3) is a member of the kinesin family known to play role in axonal transport cargo. Mutations gene have been linked severe neurodevelopmental disorders, resulting developmental delay, intellectual disability, ataxia, tremor, autism, seizures, and visual impairment. A patient who has missense mutation MAPK8IP3 (c. 1714 C>T, Arg578Cys) (R578C) manifests dystonia, gross motor delay delay. Here we show that toxic gain function which...
ABSTRACT We report the molecular characterization of a novel nucleolar protein, Nop52, and its subcellular distribution during cell cycle nucleologenesis. This protein was originally identified with human autoantibodies which were subsequently used to clone corresponding cDNA. Transfection experiments in mammalian cells have confirmed that this cDNA encodes accumulates nucleoli at periphery chromosomes. Nop52 is putative homologue yeast ribosomal RNA processing RRP1 involved pre-rRNA from...