title: HSP27 controls GATA-1 protein level during erythroid cell differentiation.
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.
authors.affiliation: INSERM U866, Faculty of Medicine and Pharmacy, University of Burgundy, 7 boulevard Jeanne d'Arc,Dijon, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: de Thonel
authors.forename: Julie
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: David
authors.initials: D
authors.lastname: Lanneau
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Selvakumar
authors.forename: Geneviève
authors.initials: G
authors.lastname: Courtois
authors.forename: Adonis
authors.initials: A
authors.lastname: Hazoume
authors.forename: Mathilde
authors.initials: M
authors.lastname: Brunet
authors.forename: Sebastien
authors.initials: S
authors.lastname: Maurel
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.forename: Jean Antoine
authors.initials: JA
authors.lastname: Ribeil
authors.forename: Yael
authors.initials: Y
authors.lastname: Zermati
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Gabet
authors.forename: Joan
authors.initials: J
authors.lastname: Boyes
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000097:blood; D019556:COS Cells; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006360:Heat-Shock Proteins; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D015850:Interleukin-6 / Q000494:pharmacology; D020014:K562 Cells; D007976:Leupeptins / Q000494:pharmacology; D018832:Molecular Chaperones; D010766:Phosphorylation / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D007093:Imidazoles; D015850:Interleukin-6; D007976:Leupeptins; D018832:Molecular Chaperones; D061988:Proteasome Inhibitors; D011725:Pyridines; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex; C093642:SB 203580; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde