ArticleNature2014
HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia.
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Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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75citing papers in PubMed, 2 pooled it
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- New Insights Into Pathophysiology of β-Thalassemia.Frontiers in medicine · 2022Pooled it
- Pooled it
- Extracellular Vesicles in Beta-Thalassemia: Phenotype-Specific Profiles and Potential Clinical Associations.Molecular diagnosis & therapy · 2026Review
- Red blood cell membrane proteome as a reporter of disease severity, transfusion impact and genetic background in transfusion-dependent β-thalassaemia.British journal of haematology · 2026Article
- Article
- ILF3 regulates erythroid differentiation: A single-cell transcriptomic analysis and cellular experiment.PloS one · 2026Article
- Erythropoiesis in health and disease: Distinguishing defective and ineffective erythropoiesis.HemaSphere · 2026Review
- Stage-specific TRIM10 expression regulates erythroid maturation.EMBO reports · 2025Article
- Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia.Haematologica · 2025Article
- In vivo deletion of a GWAS-identified Myb distal enhancer acts on Myb expression, globin switching, and clinical erythroid parameters in β-thalassemia.Scientific reports · 2025Article
- Article
- Iron-Loading Anemias.Advances in experimental medicine and biology · 2025Review
- Trans-acting genetic modifiers of clinical severity in heterozygous β-Thalassemia trait.Annals of hematology · 2024Review
- Erythropoiesis and Gene Expression Analysis in Erythroid Progenitor Cells Derived from Patients with Hemoglobin H/Constant Spring Disease.International journal of molecular sciences · 2024Article
- Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism.Pathogens (Basel, Switzerland) · 2024Article
- A newly identified gene Ahed plays essential roles in murine haematopoiesis.Nature communications · 2024Article
- Interplay between α-thalassemia and β-hemoglobinopathies: Translating genotype-phenotype relationships into therapies.HemaSphere · 2024Article
- A Review of Key Regulators of Steady-State and Ineffective Erythropoiesis.Journal of clinical medicine · 2024Review
- The interactions between ineffective erythropoiesis and ferroptosis in β-thalassemia.Frontiers in physiology · 2024Review
- Exploring the bone marrow micro environment in thalassemia patients: potential therapeutic alternatives.Frontiers in immunology · 2024Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 11 institutions in 1 country.
Jean-Benoît Arlet1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Service de Médecine Interne, Faculté de médecine Paris Descartes, Sorbonne Paris-Cité et Assistance publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 15 rue Leblanc 75908 Paris, France [3] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [4] Laboratory of Excellence GR-Ex, 75015 Paris, France [5].
Jean-Antoine Ribeil1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France [4] Département de Biothérapie, Faculté de médecine Paris Descartes, Sorbonne Paris-Cité et Assistance publique - Hôpitaux de Paris, Hôpital Necker, 149 rue de Sèvres 75015 Paris, France [5].
Flavia Guillem1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France.
Olivier NegreCommissariat à l'énergie atomique (CEA), Institute of Emerging Diseases and Innovative Therapies (iMETI), 18 Route du Panorama, 92260 Fontenay-aux-Roses, France.
Adonis Hazoume1] INSERM, unité mixte de recherche 866, Equipe labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, and Laboratoire d'Excellence Lipoprotéines et santé (LipSTIC), 21033 Dijon, France [2] University of Burgundy, Faculty of Medicine and Pharmacy, 7 boulevard Jeanne d'Arc, 21033 Dijon, France.
Guillaume Marcion1] INSERM, unité mixte de recherche 866, Equipe labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, and Laboratoire d'Excellence Lipoprotéines et santé (LipSTIC), 21033 Dijon, France [2] University of Burgundy, Faculty of Medicine and Pharmacy, 7 boulevard Jeanne d'Arc, 21033 Dijon, France.
Yves BeuzardCommissariat à l'énergie atomique (CEA), Institute of Emerging Diseases and Innovative Therapies (iMETI), 18 Route du Panorama, 92260 Fontenay-aux-Roses, France.
Michaël Dussiot1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France [4] INSERM, unité mixte de recherche 699, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Ivan Cruz Moura1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France [4] INSERM, unité mixte de recherche 699, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France [5] Faculté de médecine and Université Denis Diderot Paris VII, 5 Rue Thomas Mann, 75013 Paris, France.
Samuel DemarestCentre national de la recherche scientifique (CNRS), unité mixte de recherche 8113, Ecole Normale Supérieure de Cachan, 61 avenue du président Wilson, 94230 Cachan, France.
Isaure Chauvot de Beauchêne1] Centre national de la recherche scientifique (CNRS), unité mixte de recherche 8113, Ecole Normale Supérieure de Cachan, 61 avenue du président Wilson, 94230 Cachan, France [2] Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Campus Paris Saclay, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France.
Zakia Belaid-Choucair1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France.
Margaux Sevin1] INSERM, unité mixte de recherche 866, Equipe labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, and Laboratoire d'Excellence Lipoprotéines et santé (LipSTIC), 21033 Dijon, France [2] University of Burgundy, Faculty of Medicine and Pharmacy, 7 boulevard Jeanne d'Arc, 21033 Dijon, France.
Thiago Trovati Maciel1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France [4] INSERM, unité mixte de recherche 699, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France [5] Faculté de médecine and Université Denis Diderot Paris VII, 5 Rue Thomas Mann, 75013 Paris, France.
Christian Auclair1] Centre national de la recherche scientifique (CNRS), unité mixte de recherche 8113, Ecole Normale Supérieure de Cachan, 61 avenue du président Wilson, 94230 Cachan, France [2] Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Campus Paris Saclay, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France.
Philippe Leboulch1] Commissariat à l'énergie atomique (CEA), Institute of Emerging Diseases and Innovative Therapies (iMETI), 18 Route du Panorama, 92260 Fontenay-aux-Roses, France [2] Women's Hospital and Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA.
Stany ChretienCommissariat à l'énergie atomique (CEA), Institute of Emerging Diseases and Innovative Therapies (iMETI), 18 Route du Panorama, 92260 Fontenay-aux-Roses, France.
Luba Tchertanov1] Centre national de la recherche scientifique (CNRS), unité mixte de recherche 8113, Ecole Normale Supérieure de Cachan, 61 avenue du président Wilson, 94230 Cachan, France [2] Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Campus Paris Saclay, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France.
Véronique Baudin-CreuzaINSERM, unité mixte de recherche 779, Université Paris XI, Le Kremlin-Bicêtre, France.
Renaud SeigneuricUniversity of Burgundy, Faculty of Medicine and Pharmacy, 7 boulevard Jeanne d'Arc, 21033 Dijon, France.
Michaela Fontenay1] Laboratory of Excellence GR-Ex, 75015 Paris, France [2] Institut Cochin, INSERM, unité mixte de recherche 1016, centre national de la recherche scientifique (CNRS), unité mixte de recherche 8104, Université Paris Descartes, and Assistance publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris Centre, Hôpital Cochin, Service d'hématologie biologique, 27 rue du Faubourg Saitn-Jacques, 75014 Paris, France.
Carmen Garrido1] INSERM, unité mixte de recherche 866, Equipe labellisée Ligue contre le Cancer and Association pour la Recherche contre le Cancer, and Laboratoire d'Excellence Lipoprotéines et santé (LipSTIC), 21033 Dijon, France [2] University of Burgundy, Faculty of Medicine and Pharmacy, 7 boulevard Jeanne d'Arc, 21033 Dijon, France [3] Centre anticancéreux George François Leclerc, 1 rue professeur Marion, 21079 Dijon, France [4].
Olivier Hermine1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France [4] Service d'hématologie, Faculté de médecine Paris Descartes, Sorbonne Paris-Cité et Assistance publique - Hôpitaux de Paris Hôpital Necker, 149 rue de Sèvres, 75015 Paris, France [5].
Geneviève Courtois1] Laboratoire INSERM, unité mixte de recherche 1163, centre national de la recherche scientifique (CNRS) équipe de recherche labellisée 8254, 24 Boulevard de Montparnasse, 75015 Paris, France [2] Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Assistance publique - Hôpitaux de Paris, Hôpital Necker, 24 Boulevard de Montparnasse, 75015 Paris, France [3] Laboratory of Excellence GR-Ex, 75015 Paris, France [4].
Centre National de la Recherche Scientifique · FRInserm · FRLaboratory of Excellence GR-Ex · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRCEA Paris-Saclay - Etablissement de Fontenay-aux-roses · FRÉcole Normale Supérieure Paris-Saclay · FRInfectious Disease Models and Innovative Therapies · FRInstitut des Maladies Génétiques Imagine · FRSorbonne Paris Cité · FRUniversité de Bourgogne · FRUniversité Paris-Saclay · FR
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates. Despite extensive knowledge of the molecular defects causing β-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage. We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of maturation. Although erythroid transcription factor GATA-1, the master transcriptional factor of erythropoiesis, is a caspase-3 target, it is not cleaved during erythroid differentiation. We have shown that, in human erythroblasts, the chaperone heat shock protein70 (HSP70) is constitutively expressed and, at later stages of maturation, translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. The primary role of this ubiquitous chaperone is to participate in the refolding of proteins denatured by cytoplasmic stress, thus preventing their aggregation. Here we show in vitro that during the maturation of human β-TM erythroblasts, HSP70 interacts directly with free α-globin chains. As a consequence, HSP70 is sequestrated in the cytoplasm and GATA-1 is no longer protected, resulting in end-stage maturation arrest and apoptosis. Transduction of a nuclear-targeted HSP70 mutant or a caspase-3-uncleavable GATA-1 mutant restores terminal maturation of β-TM erythroblasts, which may provide a rationale for new targeted therapies of β-TM.
Indexed as
Erythropoiesisalpha-GlobinsApoptosisbeta-ThalassemiaBone MarrowCaspase 3Cell NucleusCells, CulturedCell SurvivalCytoplasmEnzyme ActivationErythroblastsGATA1 Transcription FactorGene Expression RegulationHSP70 Heat-Shock ProteinsHumansalpha-GlobinsCaspase 3GATA1 protein, humanGATA1 Transcription FactorHSP70 Heat-Shock Proteins
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