Overexpression of HSF2-beta inhibits hemin-induced heat shock gene expression and erythroid differentiation in K562 cells.
Acquisition of heat shock factor 2 (HSF2) DNA binding activity is accompanied by induced transcription of heat shock genes in hemin-treated K562 cells undergoing erythroid differentiation. Previous studies revealed that HSF2 consists of two alternatively spliced isoforms, HSF2-alpha and HSF2-beta, whose relative abundance is developmentally regulated and varies between different tissues. To investigate whether the molar ratio of HSF2-alpha and HSF2-beta isoforms is crucial for the activation of HSF2 and whether the HSF2 isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation, we generated cell clones expressing different levels of HSF2-alpha and HSF2-beta. We show that in parental K562 cells, the HSF2-alpha isoform is predominantly expressed and HSF2 can be activated upon hemin treatment. In contrast, when HSF2-beta is expressed at levels exceeding those of endogenous HSF2-alpha, the hemin-induced DNA binding activity and transcription of heat shock genes are repressed, whereas overexpression of HSF2-alpha results in an enhanced hemin response. Furthermore, the hemin-induced accumulation of globin, known as a marker of erythroid differentiation, is decreased in cells overexpressing HSF2-beta. We suggest that HSF2-beta acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells.
Leppä
S
S
Turku Centre for Biotechnology, University of Turku, Abo Akademi University, P. O. Box 123, FIN-20521 Turku, Finland.
Pirkkala
L
L
Saarento
H
H
Sarge
K D
KD
Sistonen
L
L
D017398:Alternative Splicing; D002454:Cell Differentiation / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000235:genetics*; D006427:Hemin / Q000502:physiology*; D006801:Humans; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D014157:Transcription Factors; C070389:HSF2 protein, human; D006427:Hemin