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

Correspondence: Dr GC Grosveld, Department of Genetics, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA. Fax: +1 901 526 2907; E-mail: gerard.grosveld@stjude.org

Received 18 February 2005; Accepted 29 April 2005; Published online 2 June 2005.

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