A5031622487- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Erythropoietin and Anemia Treatment
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Malaria Research and Control
- Cell death mechanisms and regulation
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- PARP inhibition in cancer therapy
- Complement system in diseases
- Chronic Myeloid Leukemia Treatments
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Cancer Mechanisms and Therapy
- Blood groups and transfusion
- RNA modifications and cancer
- Platelet Disorders and Treatments
- Metabolism, Diabetes, and Cancer
- Blood properties and coagulation
- RNA Interference and Gene Delivery
- FOXO transcription factor regulation
- Signaling Pathways in Disease
- Chronic Lymphocytic Leukemia Research
Institut Cochin
2013-2023
Institut des Maladies Génétiques Imagine
2023
Inserm
2010-2022
Université Paris Cité
2007-2022
Centre National de la Recherche Scientifique
2007-2022
Laboratory of Excellence GR-Ex
2013-2022
Sorbonne Paris Cité
2016-2018
Délégation Paris 5
2006-2018
Centre National pour la Recherche Scientifique et Technique (CNRST)
2018
La Ligue Contre le Cancer
2013-2016
Mass spectrometry-based proteomics now enables the absolute quantification of thousands proteins in individual cell types. We used this technology to analyze dynamic proteome changes occurring during human erythropoiesis. quantified expression 6,130 erythroid differentiation from late burst-forming units-erythroid (BFU-Es) orthochromatic erythroblasts. A modest correlation between mRNA and protein was observed. identified several with unexpected patterns cells, highlighting a breakpoint...
Two distinct genes encode the closely related signal transducer and activator of transcription proteins STAT5A STAT5B. The molecular mechanisms gene regulation by STAT5 and, particularly, requirement for both isoforms are still undetermined. Only a few target genes, among them CIS (cytokine-inducible SH2-containing protein) gene, have been identified. We cloned human studied promoter. This promoter contains four STAT binding elements organized in two pairs. By electrophoretic mobility shift...
In this report, we demonstrate that insulin receptor substrate-2 (IRS-2) is phosphorylated on tyrosine following treatment of UT-7 cells with erythropoietin. We have investigated the expression IRS-1 and IRS-2 in several cell lines erythroid and/or megakaryocytic features, observed was expressed all tested. contrast, did not detect these cells. response to erythropoietin, immediately tyrosine, maximal phosphorylation between 1 5 min. Tyrosine-phosphorylated associated phosphatidylinositol...
The binding of erythropoietin (Epo) to its receptor leads the transient phosphorylation Epo (EpoR) and activation intracellular signaling pathways. Inactivation mechanisms are simultaneously turned on, Epo-induced pathways return nearly basal levels after 30–60 min stimulation. We show that proteasomes control these inactivation mechanisms. In cells treated with proteasome inhibitors<i>N</i>-Ac-Leu-Leu-norleucinal (LLnL) or lactacystin, EpoR tyrosine (Jak2, STAT5, phosphatidylinositol...
Transferrin receptor-2 is a transmembrane protein whose expression restricted to hepatocytes and erythroid cells. has regulatory function in iron homeostasis, since its inactivation causes systemic overload. Hepatic transferrin participates sensing involved hepcidin activation, although the mechanism remains unclear. Erythroid associates with stabilizes erythropoietin receptors on erythroblast surface essential control erythrocyte production deficiency. We identified soluble form of media...
Abstract Murine-based cellular models have provided and continue to provide many useful insights into the fundamental mechanisms of erythropoiesis, as well pathophysiology inherited acquired red cell disorders. Although detailed information on aspects these is available, comprehensive proteomic data are lacking. This a critical knowledge gap, proteins effectors most biologic processes. To address this unmet need, proteomes murine lines Friend erythroleukemia (MEL), GATA1 erythroid (G1ER),...
The ribosomal protein S6 kinase (S6K) belongs to the AGC family of Ser/Thr kinases and is known be involved in regulation synthesis G(1)/S transition cell cycle. There are two forms S6K, termed S6Kalpha S6Kbeta, which have cytoplasmic nuclear splice variants. Nucleocytoplasmic shuttling has been recently proposed for S6Kalpha, based on use export inhibitor, leptomycin B. However, molecular mechanisms regulating subcellular localization S6Ks response mitogenic stimuli remain elucidated. Here...
We have shown previously that caspases were specifically involved in the differentiation of peripheral blood monocytes into macrophages while not required for monocyte dendritic cells. To identify caspase targets undergoing macrophagic differentiation, we used human monocytic leukemic cell line U937, whose induced by exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) can be prevented expression baculovirus caspase-inhibitory protein p35. A comparative two-dimensional gel proteomic...
Erythropoietic activity is known to affect iron homeostasis through regulation of the liver regulatory hormone hepcidin. To identify new factors secreted by erythroblasts that could influence hepcidin synthesis, we set up a coculture model. HuH7 hepatoma cells cocultured with primary human or erythroleukemic UT7 presented 20-to 35-fold increase gene expression. This induction was fully blunted in presence neutralizing oncostatin M antibody, demonstrating this cytokine, belonging IL-6 family...
Coenzyme A functions as a carrier of acetyl and acyl groups in living cells is essential for numerous biosynthetic, energy-yielding, degradative metabolic pathways. There are five enzymatic steps CoA biosynthesis. To date, molecular cloning enzymes involved the biosynthetic pathway mammals has been only reported pantothenate kinase. In this study, we present cDNA functional characterization synthase. It an open reading frame 563 aa encodes protein ∼60 kDa. Sequence alignments suggested that...
The stem cell factor receptor (SCF) c-Kit plays a pivotal role in regulating proliferation and survival many types. In particular, is required for early amplification of erythroid progenitors, while it must disappear from surface the entering final steps maturation an erythropoietin-dependent manner. We initially observed that imatinib (IM), inhibitor targeting tyrosine kinase activity concomitantly down-regulated expression accelerated Epo-driven differentiation erythroblasts absence SCF....
Erythropoiesis-stimulating agents are generally the first line of treatment anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated predictive value somatic mutations, and biomarkers ineffective erythropoiesis including flow cytometry RED score, serum growth-differentiation factor-15, hepcidin levels. Inclusion criteria were no prior erythropoiesis-stimulating agents, low- or intermediate-1-risk syndrome according to International Prognostic Scoring System,...
Most eukaryotic expression systems make use of host-cell nuclear transcriptional and post-transcriptional machineries. Here, we present the first generation chimeric cytoplasmic capping-prone phage polymerase (C3P3-G1) system developed by biological engineering, which generates capped polyadenylated transcripts in cytoplasm means two components. First, an artificial single-unit enzyme made fusing mRNA capping a DNA-dependent RNA polymerase. Second, specific DNA templates designed to operate...
Primary familial and congenital polycythemia is characterized by erythropoietin hypersensitivity of erythroid progenitors due to germline nonsense or frameshift mutations in the receptor gene. All so far described lead truncation C-terminal sequence that contains negative regulatory domains. Their removal presented as sufficient cause phenotype. Here we provide evidence for a new mechanism whereby presence novel sequences generated required phenotype rather than just extensive resulting from...