Opposing actions of STAT-1 and STAT-3

The signal transducers and activators of transcription (STATs) are a family of transcription factors, which were originally identified on the basis of their ability to transduce a signal from a cellular receptor into the nucleus and modulate the transcription of specific genes. Interestingly, recent studies have demonstrated that STAT-1 plays a key role in promoting apoptosis in a variety of cell types, whereas STAT-3 has an anti-apoptotic effect. Moreover, whilst STAT-3 promotes cellular proliferation and is activated in a variety of tumour cells, STAT-1 appears to have an anti-proliferative effect. Although the initially characterised signal transduction events mediated by STAT-1 and STAT-3 involve the DNA binding and transcriptional activation domains of the factor, some of their other effects appear not to require DNA binding. Therefore, STAT-1 and STAT-3 can mediate the regulation of gene transcription both by direct DNA binding and via a co-activator mechanism and despite their very similar structures, have antagonistic effects on cellular proliferation and apoptosis.