Overexpression of HSF2-β Inhibits Hemin-induced Heat Shock Gene Expression and Erythroid Differentiation in K562 Cells

• Published in: The Journal of biological chemistry Vol. 272; no. 24; p. 15293
• Main Authors: Sirpa LeppÃ, Lila Pirkkala, Helena Saarento, Kevin D. Sarge, Lea Sistonen
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 13.06.1997
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.24.15293

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-α and HSF2-β, whose relative abundance is developmentally regulated and varies between different tissues. To investigate whether the molar ratio of HSF2-α and HSF2-β 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-α and HSF2-β. We show that in parental K562 cells, the HSF2-α isoform is predominantly expressed and HSF2 can be activated upon hemin treatment. In contrast, when HSF2-β is expressed at levels exceeding those of endogenous HSF2-α, the hemin-induced DNA binding activity and transcription of heat shock genes are repressed, whereas overexpression of HSF2-α 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-β. We suggest that HSF2-β acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells.