A5052637990- Microtubule and mitosis dynamics
- Erythrocyte Function and Pathophysiology
- Ubiquitin and proteasome pathways
- Protist diversity and phylogeny
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Neonatal Health and Biochemistry
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Enzyme Structure and Function
- Genomics and Phylogenetic Studies
- Metabolism, Diabetes, and Cancer
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Protein Structure and Dynamics
- Endoplasmic Reticulum Stress and Disease
- Biomedical Research and Pathophysiology
- Genomics and Chromatin Dynamics
- Cancer Treatment and Pharmacology
- Photosynthetic Processes and Mechanisms
- Fungal and yeast genetics research
- Toxoplasma gondii Research Studies
- Diet, Metabolism, and Disease
- Glycosylation and Glycoproteins Research
HUN-REN Research Centre for Natural Sciences
2013-2024
Institute of Molecular Life Sciences
2012-2023
Hungarian Academy of Sciences
2008-2020
HUN-REN Szegedi Biológiai Kutatóközpont
2000-2008
Eötvös Loránd University
1998-2006
University of Szeged
2003-2006
University of California, San Francisco
2006
Gedeon Richter (Hungary)
2001
Institute of Haematology and Blood Transfusion
2001
Institut National de la Transfusion Sanguine
2001
The disordered tubulin polymerization promoting protein (TPPP/p25) was found to be co-enriched in neuronal and glial inclusions with α-synuclein Parkinson disease multiple system atrophy, respectively; however, co-occurrence of β-amyloid (Aβ) human brain has been recently reported, suggesting the existence mixed type pathologies that could result obstacles correct diagnosis treatment. Here we identified TPPP/p25 as an interacting partner soluble Aβ oligomers major risk factors for Alzheimer...
Previously, we have demonstrated the presence of a protein factor [tubulin polymerization perturbing (TPPP)] in brain and neuroblastoma cell but not muscle extract that uniquely influences microtubule assembly. Here describe procedure for isolation this from cytosolic fraction bovine present evidence is target both tubulin microtubules vitro. The crucial step purification cationic exchange chromatography; bound TPPP eluted at high salt concentrations, indicating basic character protein. By...
Recently, we isolated from bovine brain a protein, TPPP/p25 and identified as p25, brain-specific protein that induced aberrant tubulin assemblies. The primary sequence of this differs other proteins so far; however, it shows high homology with p25-like hypothetical sought via blast . Here, characterized the binding to by means surface plasmon resonance; kinetic parameters are follows: k on , 2.4 × 10 4 M –1 ·s ; off 5.4 –3 s K d 2.3 –7 M. This at substoichometric concentration promotes...
TPPP/p25 is a brain-specific protein, which induces tubulin polymerization and microtubule (MT) bundling enriched in Lewy bodies characteristic of Parkinson's disease [Tirián et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 13976−13981]. We identified two human gene sequences, CG1−38 p25β, encoded homologous proteins, that we termed p20 p18, respectively. These proteins display 60% identity with promoting protein/p25 (TPPP/p25); however, the N-terminal segment missing. They could be...
Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. In the present study, formation of inclusions caused mutation huntingtin protein and its relationship with changes in energy metabolism pathological were investigated both transgenic 3-nitropropionic acid-treated mouse models for HD. The HD normal mice clinically; affected brain regions identified immunohistochemistry used...
Tubulin polymerization-promoting protein (TPPP), an unfolded brain-specific interacts with the tubulin/microtubule system in vitro and vivo, is enriched human pathological brain inclusions. Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, phosphorylation of specific sites distinctly affects function TPPP. In wild type truncated form (Δ3-43TPPP) recombinant was performed by kinases involved processes. A stoichiometry 2.9 ± 0.3, 2.2 0.9 0.1 mol...
Simultaneous binding of two sequential glycolytic enzymes, phosphofructokinase and aldolase, to a microtubular network was investigated. The the microtubules its bundling activity has been previously characterized (Lehotzky, A., Telegdi, M., Liliom, K., Ovádi, J. (1993) <i>J. Biol. Chem.</i> 268, 10888–10894). Aldolase at near physiological ionic strength is weak (<i>K</i> <sub>d</sub> = 20 μm) as compared with that kinase 1 μm). interactions both enzymes are modulated by their common...
The modulatory action of Ca2+-calmodulin on multiple targets is inhibited by trifluoperazine, which competes with target proteins for calmodulin binding. structure crystallized two trifluoperazine molecules determined X-ray crystallography at 2.74 Å resolution. data together the characteristic and distinct signals obtained circular dichroism in solution allowed us to identify binding domains as well order calmodulin. Accordingly, trifluperazine C-terminal hydrophobic pocket followed...
TPPP/p25, the first representative of a new protein family, identified as brain-specific unfolded induces aberrant microtubule assemblies in vitro, suppresses mitosis Drosophila embryo and is accumulated inclusion bodies human pathological brain tissues. In this paper, we present prediction additional experimental data that validate TPPP/p25 to be member "intrinsically unstructured" family. The comparison these characteristics with alpha-synuclein tau, involved also neurodegenerative...
Abstract TPPP/p25 is a recently discovered, unstructured protein involved in brain function. It found predominantly oligodendrocytes normal but enriched neuronal and glial inclusions of Parkinson's disease other synucleinopathies. Its physiological function seems to be the dynamic stabilization microtubular ultrastructures, as well projections mature ciliary structures. We reappraise earlier belief that brain‐specific protein. have identified cloned two shorter (N‐terminal‐free) homologs...
The kinetics of dynamically interacting enzyme systems is examined, in the light increasing evidence attesting to widespread occurrence this mode organization vivo. transient time, a key phenomenological parameter for coupled reaction, expressed as function lifetime intermediate substrate. relationships between time and pseudo-first-order rate constants reaction by complexed uncomplexed species are indicative mechanism transfer (‘channelling’). In system these kinetic parameters composite...
In a Hungarian family with triosephosphate isomerase (TPI; d -glyceraldehyde-3-phosphate keto-isomerase, EC 5.3.1.1 ) deficiency, two germ-line identical, but phenotypically differing compound heterozygote brothers (one of them neurological disorder) have been identified the same very low (<5%) TPI activity and 20- or 40-fold higher erythrocyte dihydroxyacetone phosphate levels as compared normal controls. Our present studies purified hemolysates revealed binding TPI, human wild-type...
Triosephosphate isomerase (TPI) deficiency is a unique glycolytic enzymopathy coupled with neurodegeneration. Two Hungarian compound heterozygote brothers inherited the same TPI mutations (F240L and E145Stop), but only younger one suffers from In present study, we determined kinetic parameters of key enzymes including mutant for rational modelling erythrocyte glycolysis. We found that low activity in cells (lower than predicted protein level specific purified recombinant enzyme) an increase...
Tubulin polymerization promoting protein, (TPPP/p25), was identified as a brain‐specific protein. The potential function of this protein resembled that MAPs. It is mainly expressed in oligodendrocytes; however, immunopositivity also detected glial and neuronal inclusions synucleinopathies. Here, we show TPPP gene(s) are conserved the genomes ciliated organisms, but lacking from nonciliated ones. This recognition based upon homologous gene sequence analysis, silico comparative genomic...
The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of microtubule system plays a crucial role in differentiation oligodendrocytes. Here we first demonstrated by multinuclear NMR that extended segments are localized at N- C-terminals straddling flexible region. We showed affinity chromatography, fluorescence spectroscopy circular dichroism GTP binds to TPPP/p25 likely within region; neither positions nor intensities peaks assigned...
TPPP/p25, a flexible unstructured protein, binds to tubulin and induces aberrant microtubule assemblies. We identified hereby glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as new interacting partner of TPPP/p25. The immunoprecipitation affinity chromatographic experiments with bovine brain cell-free extract revealed that the interaction was salt NAD(+) sensitive while ELISA showed resistant firm association two isolated proteins. In transfected HeLa cells at low expression level...