SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells.
Human SET, a target of chromosomal translocation in human leukemia encodes a highly conserved, ubiquitously expressed, nuclear phosphoprotein. SET mediates many functions including chromatin remodeling, transcription, apoptosis and cell cycle control. We report that overexpression of SET directs differentiation of the human promonocytic cell line U937 along the dendritic cell (DC) pathway, as cells display typical morphologic changes associated with DC fate and express the DC surface markers CD11b and CD86. Differentiation occurs via a calcium-dependent mechanism involving the CaMKII and MAPK/ERK pathways. Similar responses are elicited by interferon-gamma (IFN-gamma) treatment with the distinction that IFN-gamma signaling activates the DNA-binding activity of STAT1 whereas SET overexpression does not. In addition, unlike IFN-gamma signaling, SET generated stress-induced p38/MAPK activity. Interestingly, IFN-gamma treatment transiently upregulated endogenous SET in a dose-dependent manner. These results suggest that SET is part of both IFN-gamma-mediated and stress-mediated cellular responses and that SET induces cell differentiation via calcium and MAPK/ERK pathways.
Kandilci
A
A
Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
Grosveld
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GC
D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D056488:Histone Chaperones; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D009000:Monocytes / Q000166:cytology*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D020298:U937 Cells; D015854:Up-Regulation / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C513473:SET protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases