STAT-1 and STAT-3: Closely Related Transcription Factors with Antagonistic Effects on Cell Proliferation and Apoptosis

D.   S.   Latchman; A.      Stephanou

Abstract

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. For example, induction of apoptosis by STAT-1 can be produced by the C-terminal activation domain in the absence of the DNA binding domain. This therefore, appears to involve a co-activator effect in which STAT-1 is recruited to DNA via a DNA-bound transcription factor. In this regard, it is of interest that STAT-1 but not STAT-3 has been shown to interact with p53 and enhance its growth arrest and apoptosis- inducing properties Hence, STAT-1 and STAT-3 can mediate the regulation of gene transcription both by direct DNA binding and via a coactivator mechanism and despite their very similar structures, have antagonistic effects on cellular proliferation and apoptosis

Keywords: apoptosis, protein interaction, p53, dna damage

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