Novel function of STAT1 in B cells: induction of cell death by a mechanism different from that of STAT1

Abstract: Alternate splicing of STAT1 produces two isoforms: , known as the active form, and , previously shown to act as a dominant-negative factor. Most studies have dealt with STAT1, showing its involvement in cell growth control and cell death. To examine the specific function of either isoform in cell death, a naturally STAT1-deficient human B cell line was transfected to ex-press STAT1 or STAT1. STAT1, expressed alone, enhanced cell death, potentiated the flu-darabine-induced apoptosis, and enhanced the nuclear location, the phosphorylation, and the transcriptional activity of p53. Unexpectedly, STAT1, expressed alone, induced cell death through a mechanism that was independent of the nuclear function of p53. Indeed, in STAT1-expressing B cells, p53 was stricktly cytoplasmic where it formed clusters, and there was no induc-tion of the transcriptional activity of p53. These data reveal a novel role of STAT1 in programmed cell death, which is independent of p53. J. Leukoc