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Differentiation

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Leukemia volume 19, pages 1439–1445 (2005)Cite this article

Abstract

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-γ (IFN-γ) treatment with the distinction that IFN-γ signaling activates the DNA-binding activity of STAT1 whereas SET overexpression does not. In addition, unlike IFN-γ signaling, SET generated stress-induced p38/MAPK activity. Interestingly, IFN-γ treatment transiently upregulated endogenous SET in a dose-dependent manner. These results suggest that SET is part of both IFN-γ-mediated and stress-mediated cellular responses and that SET induces cell differentiation via calcium and MAPK/ERK pathways.

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Acknowledgements

We thank Dr Youngsoo Lee for expert help with the microarray data analysis and real time RT-PCR experiments, Dr T Copeland for SET antibody, Drs Ann-Mary Hamilton-Easton and Richard Ashmun for FACS analysis, Dr Susan Magdaleno for light microscopy and Charlette Hill for secretarial assistance. This work was supported by NIH Grant CA-76480-05, Cancer Center Support CA-21765 and by the American Lebanese Syrian Associated Charities (ALSAC).

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  1. Department of Genetics and Tumor Cell Biology, Mail Stop 331, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, 38105, TN, USA

    A Kandilci & G C Grosveld

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Correspondence to G C Grosveld.

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Kandilci, A., Grosveld, G. SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells. Leukemia 19, 1439–1445 (2005). https://doi.org/10.1038/sj.leu.2403826

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