A5045140296- Signaling Pathways in Disease
- Heat shock proteins research
- Alzheimer's disease research and treatments
- Toxin Mechanisms and Immunotoxins
- Estrogen and related hormone effects
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Viral Infectious Diseases and Gene Expression in Insects
- Nerve injury and regeneration
- Prion Diseases and Protein Misfolding
- Hormonal Regulation and Hypertension
- Advanced Proteomics Techniques and Applications
- Nuclear Receptors and Signaling
- Cellular transport and secretion
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Enzyme Structure and Function
- RNA Research and Splicing
- Viral-associated cancers and disorders
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Lymphoma Diagnosis and Treatment
- Hormonal and reproductive studies
- Neuroscience and Neuropharmacology Research
- Liver physiology and pathology
Inserm
2012-2023
Université Paris-Saclay
2010-2023
Université Paris-Sud
1990-2019
Bicêtre Hospital
2016
Université Paris Cité
2015
Collège de France
1996-2003
Institut Curie
1999
Tokyo Metropolitan Institute of Medical Science
1997
The University of Tokyo
1997
Oxford University Press (United Kingdom)
1984
Significance In Alzheimer’s disease, the microtubule-associated protein Tau is invariably found in a hyperphosphorylated and aggregated form. Whether (hyper)phosphorylation can drive aggregation less clear, no precise phosphorylation pattern leading to has been described. Combining vitro assays with purified kinases rat brain extract analytical power of NMR spectroscopy, we unravel here that drives its aggregation. The results point importance this posttranslational modification Tau's...
Several mutants of the human estrogen receptor (ER) were transiently expressed in Cos 7 cells order to determine regions involved formation complexes with heat shock protein Mr approximately 90,000 (hsp 90). The cytosol non-DNA binding 8-9 S (8-9 ER) was monitored by glycerol gradient ultracentrifugation. It established that N-terminal region receptor, including two zinc fingers DNA domain (DBD), is not required for ER complexes. Conversely, deletion entire ligand (LBD) produced truncated...
Tau is a microtubule-associated protein, which widely expressed in the central nervous system, predominantly neurons, where it regulates microtubule dynamics, axonal transport, and neurite outgrowth. The aberrant assembly of hallmark several human neurodegenerative diseases, collectively known as tauopathies. They include Alzheimer’s disease, Pick’s progressive supranuclear palsy, frontotemporal dementia parkinsonism linked to chromosome 17. Several abnormalities Tau, such...
A protein of apparent molecular mass approximately 59 kDa the FK506-binding class (FKBP59) has been found associated with heat shock hsp90 included in nontransformed steroid receptor complexes and termed FKBP59-HBI (HBI for Heat 90 Binding Immunophilin). Further data analysis revealed that this immunophilin also belongs to tetratricopeptide repeat family proteins. In work, we describe hsp90-binding domain FKBP59-HBI. Density gradient centrifugation, gel filtration, immunoadsorption analyses...
The neurosteroid pregnenolone (PREG) and its chemically synthesized analog 3β-methoxypregnenolone (MePREG) bind to microtubule-associated protein 2 (MAP2) stimulate the polymerization of microtubules. PREG, MePREG, progesterone (PROG; physiological immediate metabolite PREG) significantly enhance neurite outgrowth nerve growth factor-pretreated PC12 cells. However, PROG, although it binds MAP2, does not increase immunostaining contrary PREG MePREG. Nocodazole, a microtubule-disrupting agent,...
FKBP52 (HSP56, p59, HBI) is the 59-kDa immunosuppressant FK506-binding protein and has peptidyl prolyl isomerase as well a chaperone-like activity in vitro . associates with heat shock HSP90 included steroid hormone receptor complexes vivo possesses conserved phosphorylation site for casein kinase II (CK2) that was previously shown to be associated HSP90. Here we examined whether phosphorylated by CK2 both Recombinant rabbit purified CK2. We expressed deletion mutants of determine site(s)...
The FK506 binding protein FKBP52 belongs to the large family of immunophilins and is known as a steroid receptor-associated protein. Previous data suggest that associated with motor dynein cytoskeleton during mitosis. Here we demonstrate specific direct interaction between tubulin. region located aa 267 400, which includes tetratricopeptide repeat domain, required for tubulin binding. We provide evidence prevents polymerization an 84 residue sequence in C-terminal part molecule (aa 375-458)...
Journal Article Mouse immunoglobulin genes: a bacterial plasmid containing the entire coding sequence for pre-γ 2a heavy chain Get access C. Auffray, Auffray Unite de Genie Genetique, ERA C.N.R.S. 201, Institut Pasteur28 rue du Docteur Roux, 75724 Paris Cedex 15, France Search other works by this author on: Oxford Academic PubMed Google Scholar R. Nageotte, Nageotte B. Chambraud, Chambraud F. Rougeon Nucleic Acids Research, Volume 8, Issue 6, 25 March 1980, Pages 1231–1242,...
The Tau protein is the major component of intracellular filaments observed in a number neurodegenerative diseases known as tauopathies. pathological mutant containing proline-to-leucine mutation at position 301 (P301L) leads to severe human tauopathy. Here, we assess impact FK506-binding with molecular mass ∼52 kDa (FKBP52), an immunophilin that interacts physiological Tau, on Tau-P301L activity. We identify direct interaction FKBP52 and its phosphorylated forms demonstrate FKBP52's ability...
Tau neuronal protein has a central role in neurodegeneration and is implicated Alzheimer disease development. Abnormal phosphorylation of impairs its interaction with other proteins associated dysregulation pathological conditions. Molecular mechanisms leading to hyperphosphorylation conditions are unknown. Here, we characterize by extracellular-regulated kinase (ERK2), mitogen-activated (MAPK) that responds extracellular signals. Analysis vitro phosphorylated activated recombinant ERK2...
Self-assembly of the microtubule-associated protein tau into neurotoxic oligomers, fibrils, and paired helical filaments, cell-to-cell spreading these pathological species are critical processes underlying pathogenesis Alzheimer's disease other tauopathies. Modulating self-assembly process inhibiting formation such toxic promising strategies for therapy development. A challenge in investigating vitro is that, unlike most amyloidogenic proteins, does not aggregate absence posttranslational...
The mRNA encoding mouse renin has been partially purified from total poly(A)-containing RNA of submaxillary glands male Swiss mice. Corresponding cDNAs were cloned in the Pst I site pBR322. Recombinants have characterized by differential screening and hybrid-arrested translation. DNA clone pRn3-5 used to study expression gland kidney different strains. same length (1600 nucleotides) appear be products gene. In vitro translation mRNAs blotting experiments shown that sequences are accumulated...
The formation of intraneuronal fibrillar inclusions tau protein is associated with several neurodegenerative diseases referred to as tauopathies including Alzheimer's disease (AD). A common feature these pathologies hyperphosphorylation tau, the main component assemblies such Paired Helical Filaments (PHFs). O-β-linked N-acetylglucosaminylation (O-GlcNAcylation) another important posttranslational modification involved in regulation pathophysiology. Among benefits O-GlcNAcylation, modulation...
Tauopathies, including Alzheimer's disease (AD), are neurodegenerative diseases associated with the pathologic aggregation of human brain Tau protein. Neuronal is involved in microtubule (MT) formation and stabilization. We showed previously that immunophilin FK506-binding protein MW ∼52 kDa (FKBP52) interferes this function full-length provokes a disease-related mutant Tau. To dissect molecular interaction between recombinant FKBP52 Tau, here, we study effect on functional fragment (Tau-F4,...
Human neurodegenerative diseases characterized by abnormal intraneuronal inclusions of the tau protein, or "tauopathies", include Alzheimer's disease (AD), Pick's disease, progressive supranuclear palsy, corticobasal degeneration as well fronto-te
The cytoplasmic mRNAs which are transcribed from the major late adenovirus promoter can be arranged into five 3'-coterminal families, L1 to L5. We have defined polyadenylation sites of that belong families at nucleotide level. From results, following conclusions made. (i) hexanucleotide sequence AAUAAA is present 3' end all type 2 and precedes site by 12 30 nucleotides. (ii) Between one three A residues in genomic site. (iii) with composition (T)n (A)p (T)q (n, p, q greater than or equal 1)...
Defects of autophagy-lysosomal protein degradation are thought to contribute the pathogenesis several neurodegenerative diseases, and accumulation aggregation prone proteins such as MAPT/Tau in Alzheimer disease (AD). We previously showed localization immunophilin FKBP4/FKBP52 lysosomal system healthy human neurons suggesting its possible role lysosome function. also that decreased FKBP4 levels AD brain correlate with abnormal MAPT aggregation. In this study, we demonstrate decrease a...