Abstract
In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anisomycin / pharmacology
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Cell Differentiation*
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Erythroid Precursor Cells / metabolism*
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism*
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Hemin / pharmacology
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Humans
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JNK Mitogen-Activated Protein Kinases
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K562 Cells
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MAP Kinase Kinase 4*
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MAP Kinase Kinase 7
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Mitogen-Activated Protein Kinase Kinases / metabolism*
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism*
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Protein Isoforms
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / metabolism
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Staurosporine / pharmacology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Enzyme Inhibitors
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Heat-Shock Proteins
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Protein Isoforms
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Proto-Oncogene Proteins c-jun
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Transcription Factors
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HSF2 protein, human
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Anisomycin
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Hemin
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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MAP Kinase Kinase 7
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MAP2K4 protein, human
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MAP2K7 protein, human
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Mitogen-Activated Protein Kinase Kinases
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Staurosporine