A5078455552- Microtubule and mitosis dynamics
- Metabolism and Genetic Disorders
- Cancer, Hypoxia, and Metabolism
- Parkinson's Disease Mechanisms and Treatments
- Enzyme Structure and Function
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Mitochondrial Function and Pathology
- Hemoglobin structure and function
- Erythrocyte Function and Pathophysiology
- Sirtuins and Resveratrol in Medicine
- Histone Deacetylase Inhibitors Research
- Cellular transport and secretion
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Genetic Neurodegenerative Diseases
- Protein Degradation and Inhibitors
- Neonatal Health and Biochemistry
- Amino Acid Enzymes and Metabolism
- Biochemical Acid Research Studies
- Alzheimer's disease research and treatments
- Photosynthetic Processes and Mechanisms
- Diet, Metabolism, and Disease
- Autophagy in Disease and Therapy
- Mass Spectrometry Techniques and Applications
HUN-REN Research Centre for Natural Sciences
2014-2024
Institute of Molecular Life Sciences
2014-2023
Hungarian Academy of Sciences
2010-2020
Istituto Ortopedico Galeazzi
2020
University of Messina
2020
Universitat Autònoma de Barcelona
2020
Lund University
2020
Széchenyi István University
2013
In-Q-Tel
2008-2011
Eötvös Loránd University
1998-2010
Abstract Sirtuins are a highly conserved class of NAD + -dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis cancer, inflammation and neurodegeneration, which makes modulation activity promising strategy for pharmaceutical intervention. A rational basis development optimized inhibitors is lacking so far. Here we present high-resolution structures complex with selective drug-like that show unique inhibitory mechanism. Potency unprecedented selectivity...
Here we report the development of a proteolysis targeting chimera (PROTAC) based on combination unique features sirtuin rearranging ligands (SirReals) as highly potent and isotype-selective Sirt2 inhibitors with thalidomide, bona fide cereblon ligand. For first time, formation PROTAC by Cu(I)-catalyzed cycloaddition thalidomide-derived azide to an alkynylated inhibitor. This well versatile linking strategy can be readily adapted other targets. In HeLa cells, our SirReal-based induced...
Abstract Cancer cells often fail to respond stimuli that normally activate their intrinsic apoptotic machinery. Moreover, they are able adapt hypoxia by changing glycolytic rate. Pyruvate kinase (PK) is a rate-limiting enzyme in glycolysis converted less active dimer form of PKM2 isoenzyme during oncogenesis. Here, we show both somatostatin and the structural analogue TT-232 interact with PKM subtype. We further translocated nucleus response different agents. Nuclear translocation sufficient...
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...
Abstract TPPP/p25, a recently identified tubulin polymerization‐promoting protein (TPPP), is expressed mainly in myelinating oligodendrocytes of the CNS. Here, we show that TPPP/p25 strongly upregulated during differentiation primary oligodendrocyte cells as well CG‐4 cell line. The microRNA expression profile before and after induction was established revealed differential regulation limited subset microRNAs. miR‐206, predicted to target not detected oligodendrocytes. Overexpression miR‐206...
TPPP/p25 (tubulin polymerization-promoting protein/p25) is an unstructured protein that induces microtubule polymerization in vitro and aligned along the network transfected mammalian cells. In normal human brain, expressed predominantly oligodendrocytes, where its expression proved to be crucial for their differentiation process. Here we demonstrated of HeLa cells, doxycycline-inducible CHO10 oligodendrocyte CG-4 cells promoted acetylation alpha-tubulin at residue Lys-40, whereas...
The possibility of interaction between purified rabbit muscle aldolase and D-glyceraldehyde-3-phosphate dehydrogenase was studied by rapid kinetic methods, analyzing the kinetics consecutive reaction catalyzed coupled enzyme system. Km intermediary product, glyceraldehyde 3-phosphate, produced determined in for glyceraldehyde-3-phosphate dehydrogenase. Its value corresponds to that aldehyde (active) form although given conditions leads diol interconversion is faster than enzymic We suggest...
Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and substrate proteins. Dysregulation human Sirt2 (hSirt2) activity has been associated with pathogenesis cancer, inflammation, neurodegeneration, which makes modulation hSirt2 a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently discovered by us as highly potent isotype-selective inhibitors....
Abstract Sirtuins are NAD + ‐dependent protein deacylases that cleave off acetyl groups, as well other acyl from the ɛ‐amino group of lysines in histones and substrate proteins. Dysregulation human Sirt2 activity has been associated with pathogenesis cancer, inflammation, neurodegeneration, thus making a promising target for pharmaceutical intervention. Here, based on crystal structure complex an optimized sirtuin rearranging ligand (SirReal) shows improved potency, water solubility,...
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...
Polarization of fluorescence measurements aldolase and D-glyceraldehyde-3-phosphate dehydrogenase labeled with fluorescein isothiocyanate have been used to detect the possible formation a soluble complex between proteins. The results suggest an interaction apparent dissociation constant 3 X 10(-7) M stoichiometry two tetramers bound per tetramer dehydrogenase.
Abstract Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) located in OG aggregates oligodendroglial cytoplasmic inclusions multiple atrophy. We developed a novel monoclonal anti‐TPPP/p25 antibody to quantify different subtypes...
The linked equilibria involved in the binding of phosphofructokinase (EC 2.7.1.11, ATP:D-fructose-6-phosphate 1-phosphotransferase) to tubulin and microtubules were studied at high ionic strength vitro. concentration-dependent dissociation was analyzed absence presence or microtubules, kinase dimer compared. Enzyme activity inhibited by both microtubules: relative inhibition increased with decreasing enzyme concentration. complex formation between demonstrated means fluorescent anisotropy....
Recently we identified TPPP/p25 (tubulin polymerization promoting protein/p25) as a brain-specific unstructured protein that induced aberrant microtubule assemblies and ultrastructure in vitro new marker for Parkinson's disease other synucleopathies. In this paper the structural functional consequences of are characterized to elucidate relationship between pathological phenomena. We show at low expression levels EGFP-TPPP/p25 specifically colocalizes with network HeLa NRK cells. found...