HSP27 controls GATA-1 protein level during erythroid cell differentiation

• Published in: Blood Vol. 116; no. 1; pp. 85 - 96
• Main Authors: de Thonel, Aurelie, Vandekerckhove, Julie, Lanneau, David, Selvakumar, Subramaniam, Courtois, Geneviève, Hazoume, Adonis, Brunet, Mathilde, Maurel, Sebastien, Hammann, Arlette, Ribeil, Jean Antoine, Zermati, Yael, Gabet, Anne Sophie, Boyes, Joan, Solary, Eric, Hermine, Olivier, Garrido, Carmen
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 08.07.2010; Americain Society of Hematology; American Society of Hematology
• Subjects: Animals; Antigens, CD34 - blood; Biological and medical sciences; Cell Differentiation; Cell Nucleus - metabolism; Cells, Cultured; Chlorocebus aethiops; COS Cells; Erythroid Cells - cytology; Erythroid Cells - drug effects; Erythroid Cells - metabolism; GATA1 Transcription Factor - genetics; GATA1 Transcription Factor - metabolism; Heat-Shock Proteins; HeLa Cells; Hematologic and hematopoietic diseases; HSP27 Heat-Shock Proteins - genetics; HSP27 Heat-Shock Proteins - metabolism; Humans; Imidazoles - pharmacology; Immunoblotting; Interleukin-6 - pharmacology; K562 Cells; Leupeptins - pharmacology; Life Sciences; Medical sciences; Molecular Chaperones; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Proteasome Endopeptidase Complex - metabolism; Proteasome Inhibitors; Protein Binding; Pyridines - pharmacology; RNA Interference; Transforming Growth Factor beta - pharmacology; Ubiquitination - drug effects; Erythropoiesis; Signal transduction; Heat choc protein 27; Erythroid cell; Hematology; Heat shock protein; Cell differentiation; Transcription factor GATA1
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-09-241778

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.