Novel function of STAT1beta in B cells: induction of cell death by a mechanism different from that of STAT1alpha.

Alternate splicing of STAT1 produces two isoforms: alpha, known as the active form, and beta, previously shown to act as a dominant-negative factor. Most studies have dealt with STAT1 alpha, 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 express STAT1 alpha or STAT1 beta. STAT1 alpha, expressed alone, enhanced cell death, potentiated the fludarabine-induced apoptosis, and enhanced the nuclear location, the phosphorylation, and the transcriptional activity of p53. Unexpectedly, STAT1 alpha, expressed alone, induced cell death through a mechanism that was independent of the nuclear function of p53. Indeed, in STAT1 beta-expressing B cells, p53 was stricktly cytoplasmic where it formed clusters, and there was no induction of the transcriptional activity of p53. These data reveal a novel role of STAT1 beta in programmed cell death, which is independent of p53. J. Leukoc. Biol. 84: 1604-1612; 2008.