STAT1 and STAT3:Opposing Roles in Cell Death and Cell Cycle Regulation
Anastasis Stephanou, R. A. Knight and D.S. Latchman
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. More recent studies have demonstrated that STAT1 also plays a key role in promoting apoptosis in a variety of cell types and therefore functions as a tumour suppressor, whereas the related STAT3 has an anti‑apoptotic effect. Moreover, whilst STAT3 promotes cellular proliferation and is activated in a variety of tumour cells, STAT1 appears to have an anti‑proliferative effect. Although the initially characterised signal transduction events mediated by STAT1 and STAT3 involve the DNA binding and transcriptional activation domains of the factor, some of their other effects appear not to require DNA binding. Therefore, STAT1 and STAT3 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.