1. HSP27 controls GATA-1 protein level during erythroid cell differentiation
- Author
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Subramaniam Selvakumar, Joan Boyes, Olivier Hermine, Arlette Hammann, David Lanneau, Mathilde Brunet, Geneviève Courtois, Eric Solary, Julie Vandekerckhove, Aurélie de Thonel, Anne Sophie Gabet, J.-A. Ribeil, Yael Zermati, Sebastien Maurel, Adonis Hazoumé, Carmen Garrido, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut International de Paléoprimatologie, Paléontologie Humaine : Evolution et Paléoenvironnement (IPHEP), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Groupe français des myéloplastes and groupe ouest est des leucemies aigües myéloïde (SERVICE DES MALADIES DU SANG), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instituto Andaluz de Ciencias de la Tierra (IACT), Consejo Superior de Investigaciones Científicas [Spain] (CSIC)-Universidad de Granada (UGR), Slama, Catherine, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad de Granada (UGR), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut International de Paléoprimatologie, Paléontologie Humaine : Evolution et Paléoenvironnement ( IPHEP ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Groupe français des myéloplastes and groupe ouest est des leucemies aigües myéloïde ( SERVICE DES MALADIES DU SANG ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Instituto Andaluz de Ciencias de la Tierra ( IACT ), and Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -Universidad de Granada ( UGR )
- Subjects
Leupeptins ,Pyridines ,[SDV]Life Sciences [q-bio] ,Cellular differentiation ,Cell ,HSP27 Heat-Shock Proteins ,Antigens, CD34 ,Biochemistry ,p38 Mitogen-Activated Protein Kinases ,0302 clinical medicine ,Transforming Growth Factor beta ,hemic and lymphatic diseases ,Chlorocebus aethiops ,GATA1 Transcription Factor ,Phosphorylation ,ComputingMilieux_MISCELLANEOUS ,Cells, Cultured ,Heat-Shock Proteins ,0303 health sciences ,biology ,Imidazoles ,Cell Differentiation ,Hematology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,embryonic structures ,COS Cells ,RNA Interference ,Signal transduction ,Proteasome Inhibitors ,Protein Binding ,Proteasome Endopeptidase Complex ,Immunology ,Immunoblotting ,03 medical and health sciences ,Hsp27 ,Erythroid Cells ,Heat shock protein ,medicine ,Animals ,Humans ,Transcription factor ,030304 developmental biology ,Cell Nucleus ,Interleukin-6 ,Ubiquitination ,Cell Biology ,Transforming growth factor beta ,Molecular biology ,Chaperone (protein) ,biology.protein ,K562 Cells ,HeLa Cells ,Molecular Chaperones - Abstract
Heat shock protein 27 (HSP27) is a chaperone whose cellular expression increases in response to various stresses and protects the cell either by inhibiting apoptotic cell death or by promoting the ubiquitination and proteasomal degradation of specific proteins. Here, we show that globin transcription factor 1 (GATA-1) is a client protein of HSP27. In 2 models of erythroid differentiation; that is, in the human erythroleukemia cell line, K562 induced to differentiate into erythroid cells on hemin exposure and CD34+ human cells ex vivo driven to erythroid differentiation in liquid culture, depletion of HSP27 provokes an accumulation of GATA-1 and impairs terminal maturation. More specifically, we demonstrate that, in the late stages of the erythroid differentiation program, HSP27 is phosphorylated in a p38-dependent manner, enters the nucleus, binds to GATA-1, and induces its ubiquitination and proteasomal degradation, provided that the transcription factor is acetylated. We conclude that HSP27 plays a role in the fine-tuning of terminal erythroid differentiation through regulation of GATA-1 content and activity.
- Published
- 2010