Overexpression of HSF2-beta inhibits hemin-induced heat shock gene expression and erythroid differentiation in K562 cells

S Leppä, L Pirkkala, H Saarento, K D Sarge, L Sistonen

Research output: Contribution to journalArticleScientificpeer-review

41 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)15293-8
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number24
DOIs
Publication statusPublished - 13 Jun 1997
MoE publication typeA1 Journal article-refereed

Keywords

  • Alternative Splicing
  • Cell Differentiation/physiology
  • Erythrocytes/cytology
  • Gene Expression Regulation/physiology
  • Heat-Shock Proteins/genetics
  • Hemin/physiology
  • Humans
  • Transcription Factors/genetics
  • Tumor Cells, Cultured

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