Hemin-induced transcriptional activation of the HSP70 gene during erythroid maturation in K562 cells is due to a heat shock factor-mediated stress response.
Hemin-induced differentiation of the human erythroleukemia cell line K562 results in the expression and accumulation of erythroid-specific gene products such as embryonic and fetal hemoglobins and the elevated synthesis of the major heat shock protein HSP70. This activity was suggested to represent activation of a heat shock gene during erythroid maturation independent of stress induction. In this study, we demonstrate that hemin induces the transcription of two members of the human HSP70 gene family, HSP70 and GRP78 (BiP). However, the induction of HSP70 by hemin showed characteristics consistent with the molecular events associated with a heat shock or stress response. The increase in HSP70 gene transcription was accompanied by induction of the stress-induced form of the heat shock transcription factor. Moreover, a heat shock element was required for the hemin responsiveness of chimeric heat shock promoter-chloramphenicol acetyltransferase genes transiently expressed in transfected K562 cells.
Theodorakis
N G
NG
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Zand
D J
DJ
Kotzbauer
P T
PT
Williams
G T
GT
Morimoto
R I
RI
D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000032:analysis; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D006360:Heat-Shock Proteins / Q000235:genetics*; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000502:physiology*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D018832:Molecular Chaperones; D014157:Transcription Factors / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014157:Transcription Factors; D006418:Heme; D006427:Hemin; D015500:Chloramphenicol O-Acetyltransferase