TY - JOUR
T1 - HSP27 controls GATA-1 protein level during erythroid cell differentiation
AU - De Thonel, Aurelie
AU - Vandekerckhove, Julie
AU - Lanneau, David
AU - Selvakumar, Subramaniam
AU - Courtois, Geneviève
AU - Hazoume, Adonis
AU - Brunet, Mathilde
AU - Maurel, Sebastien
AU - Hammann, Arlette
AU - Ribeil, Jean Antoine
AU - Zermati, Yael
AU - Gabet, Anne Sophie
AU - Boyes, Joan
AU - Solary, Eric
AU - Hermine, Olivier
AU - Garrido, Carmen
PY - 2010/7/8
Y1 - 2010/7/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77955877483&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-09-241778
DO - 10.1182/blood-2009-09-241778
M3 - Article
C2 - 20410505
AN - SCOPUS:77955877483
SN - 0006-4971
VL - 116
SP - 85
EP - 96
JO - Blood
JF - Blood
IS - 1
ER -